DAUNOrubicin (Monograph)

Brand names: Cerubidine, DaunoXome
Drug class: Antineoplastic Agents
VA class: AN200
Chemical name: (7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
Molecular formula: C₂₇H₂₉NO₁₀
CAS number: 20830-81-3

Medically reviewed by Drugs.com on Sep 23, 2024. Written by ASHP.

Introduction

Antineoplastic agent; anthracycline glycoside antibiotic.^{133 127}

Uses for DAUNOrubicin

Acute Lymphocytic Leukemia (ALL)

Conventional daunorubicin hydrochloride: Remission induction (in combination with other antineoplastic agents) in childhood or adult ALL.^{126 127 128 129 130 131 132 215}

In non-high-risk childhood ALL, combination therapy with an asparaginase preparation, a corticosteroid (dexamethasone or prednisone), and vincristine is used as an induction regimen.¹²⁸ Intensive induction regimens with ≥4 drugs, including an anthracycline (e.g., daunorubicin), an asparaginase preparation, a corticosteroid, and vincristine, with or without cyclophosphamide, may improve event-free survival but cause greater toxicity.¹²⁸ Some clinicians reserve 4- or 5-drug regimens for patients with high-risk childhood ALL; others elect to use such regimens for all patients with childhood ALL regardless of presenting features.¹²⁸

In adults, induction regimens typically include an anthracycline, vincristine, and prednisone; some regimens also add other drugs (e.g., an asparaginase preparation, cyclophosphamide).¹²⁹

Various regimens have been used in combination therapy, and comparative efficacy is continually being evaluated.^{126 127 128 129 130 131 132}

Other regimens are preferred in certain subsets of patients with ALL (e.g., B-cell ALL, T-cell ALL, Philadelphia chromosome-positive ALL);^{129 131} consult specialized references and experts for additional information.^f

Acute Myeloid Leukemia (AML)

Conventional daunorubicin hydrochloride: Used in combination with other antineoplastic agents for the treatment of AML in adults.^{125 127 154} Cytarabine with either daunorubicin or idarubicin is a regimen of choice for remission induction in AML.^{127 154}

Consolidation chemotherapy^{† [off-label]} typically consists of a cytarabine-based regimen similar to that used in induction therapy administered over a short-term period following induction of complete remission.¹⁵⁴ Duration of consolidation chemotherapy has ranged from one to ≥4 cycles;^{154 157 160 161} however, optimal consolidation chemotherapy regimen (including dosage, schedules, and duration) not established.¹⁵⁴ Maintenance therapy for AML generally not recommended.¹⁵⁴

Chronic Myelogenous Leukemia (CML)

Conventional daunorubicin hydrochloride: Has been used with other antineoplastic agents in the treatment of accelerated or blast-phase CML^{† [off-label]}.^{127 h}

AIDS-related Kaposi’s Sarcoma

Liposomal daunorubicin citrate: First-line therapy for advanced AIDS-related Kaposi’s sarcoma;^{127 133 189} not recommended for early stages of the disease.¹³³ Liposomal anthracycline (daunorubicin or doxorubicin) is the first-line therapy of choice for advanced AIDS-related Kaposi’s sarcoma.^{127 189}

Comparative efficacy of liposomal daunorubicin citrate relative to liposomal doxorubicin not established,^{133 134 135 136} but liposomal daunorubicin appears to be better tolerated than and comparably effective to combination chemotherapy (e.g., conventional doxorubicin, bleomycin, and vincristine) for the management of advanced AIDS-related Kaposi’s sarcoma.^{135 189}

DAUNOrubicin Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.^{133 215}

• Daunorubicin as a single-entity preparation not interchangeable with the fixed liposomal combination of daunorubicin and cytarabine (daunorubicin/cytarabine liposomal; Vyxeos).²¹⁷ To avoid dosing errors, confirm correct drug name, formulation, and dose prior to preparation and administration.²¹⁷

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer IV into a rapidly flowing IV infusion.^{125 215} Extremely irritating to tissues; do not administer IM or sub-Q.^{125 215} Avoid extravasation.¹³³ (See Local Effects under Cautions.)

If skin or mucosal contact occurs, immediately wash affected area(s) thoroughly with soap and water.^{125 215}

Observe IV injection site and surrounding areas for infiltration and vein irritation during administration; if signs or symptoms of extravasation occur, stop infusion and restart at another site.^f

Conventional Daunorubicin Hydrochloride

After dilution of desired dose in syringe, inject into the tubing or sidearm of a rapidly flowing IV infusion of 0.9% sodium chloride or 5% dextrose injection.²¹⁵

Following injection, some clinicians recommend flushing the vein with the running IV infusion for 2–5 minutes and/or injecting 5–10 mL of IV solution into sidearm to flush any remaining drug from the tubing.^f

Avoid small veins, swollen or edematous extremities, and areas overlying joints and tendons as injection sites.^f

Liposomal Daunorubicin Citrate

Administer by IV infusion; do not use inline filters.¹³³

Reconstitution of Conventional Daunorubicin Hydrochloride

Add 4 mL of sterile water for injection to vial containing 20 mg daunorubicin lyophilized powder and gently agitate until contents completely dissolve; resultant solution contains 5 mg/mL.¹²⁵

Dilution of Conventional Daunorubicin Hydrochloride

Withdraw desired dose of commercially available or reconstituted solution into a syringe containing 10–15 mL of 0.9% sodium chloride injection.^{125 215}

Dilution of Liposomal Daunorubicin Citrate

Must dilute prior to administration; observe strict aseptic technique since product does not contain preservative or bacteriostatic agent.¹³³ Withdraw appropriate dose of commercially available injection (concentration: 2 mg/mL) from vial with sterile syringe and transfer into a small-volume PVC container containing an equivalent volume of dextrose 5% injection to provide a solution containing 1 mg/mL.¹³³

Do not use diluents containing preservatives (e.g., benzyl alcohol) or other diluents; do not mix other drugs with the solution.¹³³

Rate of Administration of Conventional Daunorubicin Hydrochloride

Inject over 2–3 minutes into the tubing or sidearm of a rapidly flowing IV infusion.^{125 215}

Rate of Administration of Liposomal Daunorubicin Citrate

Administer by IV infusion over 60 minutes.¹³³

Dosage

Available as daunorubicin hydrochloride (conventional) or daunorubicin citrate encapsulated in liposomes (liposomal); dosage expressed in terms of daunorubicin.^{133 215}

Conventional daunorubicin hydrochloride: Optimize results and minimize adverse effects by basing dose on clinical and hematologic response, patient tolerance, and other chemotherapy or irradiation being used.^f

Consult published protocols for dosages in combination regimens and method and sequence of administration.^f

Pediatric Patients

ALL

Representative Dosage Schedule and Combination Therapy for Remission Induction

IV

Conventional daunorubicin hydrochloride: For children <2 years of age or with body surface area <0.5 m², calculate daunorubicin dosage (1 mg/kg) on basis of body weight rather than body surface area.^{125 215} Consult published protocols for dosages for prednisone, vincristine, or other antineoplastic agents in these children.

Conventional daunorubicin hydrochloride: In children ≥2 years of age and with body surface area ≥0.5 m², 25 mg/m² IV on day 1 every week, in combination with vincristine (1.5 mg/m² IV on day 1 every week) and prednisone (40 mg/m² orally daily).^{125 215} Generally, complete remission is obtained within 4 such courses; however, if after 4 courses, the patient is in partial remission, an additional 1 or 2 (if necessary) courses may be given in effort to obtain complete remission.^{125 215}

Other regimens have been used; dosage generally has ranged from 25–45 mg/m², with frequency of administration dependent on specific regimen employed; consult published protocols.^f

Consolidation and Cumulative Dosage

Initiate appropriate consolidation therapy after induction of a complete remission.^f

Total dosage administered should take into account previous or concomitant therapy with other potentially cardiotoxic agents or with related drugs (e.g., doxorubicin).¹²⁵ (See Myocardial Toxicity in Boxed Warning and also Prescribing Limits under Dosage and Administration.)

Adults

ALL

Representative Dosage Schedule and Combination Therapy for Remission Induction

IV

Conventional daunorubicin hydrochloride: 45 mg/m² IV on days 1, 2, and 3, in combination with vincristine (2 mg IV on days 1, 8, and 15), prednisone (40 mg/m² orally daily on days 1–22, then tapered between days 22–29), and asparaginase (500 units/kg IV daily for 10 days on days 22–32).²¹⁵

Consolidation and Cumulative Dosage

Initiate appropriate consolidation therapy after induction of a complete remission.^f

Total dosage administered should take into account previous or concomitant therapy with other potentially cardiotoxic agents or with related drugs (e.g., doxorubicin).¹²⁵ (See Myocardial Toxicity in Boxed Warning and also Prescribing Limits under Dosage and Administration.)

AML

Representative Dosage Schedule and Combination Therapy for Remission Induction

IV

Conventional daunorubicin hydrochloride: Adults <60 years of age: 45 mg/m² IV daily on days 1, 2, and 3 of first course and on days 1 and 2 of subsequent courses, in combination with cytarabine (100 mg/m² IV daily for 7 days for first course and for 5 days for subsequent courses).^{125 215}

Conventional daunorubicin hydrochloride: Adults ≥60 years of age: 30 mg/m² IV daily on days 1, 2, and 3 of first course and on days 1 and 2 of subsequent courses, in combination with cytarabine (100 mg/m² IV daily for 7 days of first course and for 5 days for subsequent courses).^{125 215} (Daunorubicin dosage reduction may not be appropriate if optimal supportive care is available.²¹⁵ )

Attainment of normal-appearing bone marrow may require up to 3 courses of induction therapy; evaluation of bone marrow following recovery from previous course determines whether additional course is required.^{125 215}

Consolidation and Cumulative Dosage

Initiate appropriate consolidation therapy after induction of a complete remission.^f

Total dosage administered should take into account previous or concomitant therapy with other potentially cardiotoxic agents or with related drugs (e.g., doxorubicin).¹²⁵ (See Myocardial Toxicity in Boxed Warning and also Prescribing Limits under Dosage and Administration.)

Advanced AIDS-related Kaposi’s Sarcoma

First-line Therapy

IV

Liposomal daunorubicin citrate: 40 mg/m² IV every 2 weeks.¹³³

Perform blood cell counts before each dose; if absolute granulocyte count <750/mm³, withhold therapy until counts exceed this level.¹³³

Continue treatment until disease progression occurs (e.g., based on best response achieved, new visceral sites of involvement or progression of visceral disease, development of ≥10 new cutaneous lesions or a 25% increase in number of lesions compared with baseline, a change in character of ≥25% of all previously counted flat to raised lesions, increased surface area of indicator lesions) or until other complications of HIV disease preclude continuation.¹³³

Prescribing Limits

Pediatric Patients

Conventional Daunorubicin Hydrochloride

IV

Children <2 years of age: Incidence of myocardial toxicity increases with total cumulative dosage >10 mg/kg.²¹⁵

Children >2 years of age: Incidence of myocardial toxicity increases with total cumulative dosage >300 mg/m².²¹⁵

Adults

Conventional Daunorubicin Hydrochloride

IV

Incidence of myocardial toxicity increases with total cumulative dosage >400–550 mg/m².^{125 215} (See Cardiotoxicity under Cautions.)

Special Populations

Hepatic Impairment

Conventional or Liposomal Daunorubicin

In patients with serum bilirubin concentrations of 1.2–3 mg/dL, administer 75% of usual daily dose; in patients with serum bilirubin concentrations >3 mg/dL, administer 50% of usual dose.^{125 133 215}

Renal Impairment

Conventional or Liposomal Daunorubicin

In patients with serum creatinine concentrations >3 mg/dL, administer 50% of usual dose.^{125 133 215}

Cautions for DAUNOrubicin

Contraindications

• Hypersensitivity to daunorubicin or any ingredient in the formulation.^{133 215}

Warnings/Precautions

Warnings

Hematologic Effects

Myelosuppression, manifested principally by severe leukopenia and thrombocytopenia, occurs in all patients receiving therapeutic dosages of conventional daunorubicin hydrochloride; infection or hemorrhage may occur.¹²⁵ Leukocyte and platelet nadirs usually occur within 10–14 days after administration, with return to normal levels during the third week.^{215 f}

In patients with AIDS-related Kaposi’s sarcoma receiving liposomal daunorubicin citrate, myelosuppression, mainly granulocytopenia (possibly severe and/or associated with fever; infection may result), is principal dose-limiting toxicity; lesser effect observed on platelets and erythroid cells.^{133 164}

Carefully monitor hematologic status during therapy; determine leukocyte, platelet, and erythrocyte counts prior to and at frequent intervals during therapy.^{133 125} Evaluate bone marrow function to guide treatment and allow sufficient time for bone marrow recovery between courses of conventional daunorubicin.^{215 f} If absolute granulocyte count <750/mm³ before scheduled dose of liposomal daunorubicin, withhold therapy until counts exceed this level.¹³³

Persistent, severe myelosuppression may result in superinfection or hemorrhage.²¹⁵ Severe hematologic toxicity may require supportive therapy, antibiotics for infections, and blood product transfusions.^f Carefully observe patients with HIV infection and immunosuppression for intercurrent or opportunistic infections.¹³³

Do not initiate conventional daunorubicin in patients with preexisting drug-induced myelosuppression unless treatment benefit warrants risk.^{125 215}

Cardiotoxicity

Risk of cardiotoxicity during or months to years after therapy; requires special attention and long-term periodic evaluation of cardiac function.^{125 133 215}

Preexisting cardiac disease and/or previous anthracycline (e.g., doxorubicin, epirubicin) therapy increase risk of daunorubicin-induced cardiotoxicity; carefully consider risks before initiation of therapy.^{125 133 215}

Infants and children appear to be at greater risk of anthracycline-induced cardiotoxicity.^{125 215} Impaired left ventricular systolic performance, reduced contractility, CHF, or death reported in pediatric patients receiving anthracycline therapy; appear to be dose-dependent and aggravated by thoracic irradiation.²¹⁵

Potentially fatal CHF may occur during therapy or months to years after termination of therapy.^{125 215} With conventional daunorubicin, incidence of myocardial toxicity (e.g., CHF) is increased at cumulative dosages >550 mg/m² (>400 mg/m² in patients who have received radiation that encompassed the heart), >300 mg/m² in children >2 years of age, or >10 mg/kg in children <2 years of age.^{125 215}

With liposomal daunorubicin, CHF reported at cumulative dose of 340 mg/m² in at least 1 patient with AIDS-related Kaposi’s sarcoma; in a limited number of patients, decreases in left ventricular ejection fraction occurred at median cumulative dose of 320 mg/m² (range: 200–2100 mg/m²).¹³³ Other serious adverse cardiac effects reported with liposomal daunorubicin include pericardial effusion, pericardial tamponade, ventricular extrasystoles, cardiac arrest, sinus tachycardia, atrial fibrillation, pulmonary hypertension, MI, supraventricular tachycardia, and angina pectoris.¹³³ Further study and experience needed to determine relative risk of anthracycline-induced cardiotoxicity associated with liposomal versus conventional daunorubicin.²⁰⁹ Previous therapy with anthracyclines (doxorubicin >300 mg/m² or equivalent) may increase risk of cardiotoxicity with liposomal daunorubicin.¹³³

Early clinical diagnosis of drug-induced CHF and prompt initiation of treatment are essential for optimizing response to supportive therapy.^{125 215}

In determining total daunorubicin dose in adults and children, consider any previous or concomitant therapy with other anthracyclines (e.g., doxorubicin) or with other potentially cardiotoxic drugs.¹²⁵ Do not use daunorubicin in patients who have previously received maximum recommended cumulative dose of doxorubicin or daunorubicin.^{125 215} (See Doxorubicin under Interactions.)

No completely reliable method exists to predict which patients will develop drug-induced CHF. ECG and/or determination of ejection fraction recommended before each course of conventional daunorubicin; if decrease ≥30% in limb lead QRS voltage in ECG (associated with substantial risk of drug-induced cardiomyopathy) or decrease in systolic ejection fraction from pretreatment baseline occurs, weigh benefits against cardiac risks.^{125 215}

The manufacturer of liposomal daunorubicin recommends evaluation of cardiac function (e.g., history of previous cardiac disease, physical examination) before each course of therapy and determination of left ventricular ejection fraction at total cumulative doses of 320 mg/m² and every 160 mg/m² thereafter (before therapy and every 160 mg/m² in patients with preexisting cardiac disease and/or those who have received previous anthracycline therapy [doxorubicin >300 mg/m² or equivalent] or radiation that encompassed the heart).¹³³

Pericarditis-myocarditis, unrelated to dose, reported rarely.^{125 215}

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.^{125 133 215} Avoid pregnancy during therapy.^{125 133}

Because of potential benefits, use during pregnancy may be acceptable in certain conditions (e.g., life-threatening situations, severe disease for which safer drugs cannot be used or are ineffective) despite possible risks to the fetus.^{125 213 214}

If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.^{125 133 215}

Local Effects

Conventional daunorubicin hydrochloride: Extravasation during infusion may cause severe local tissue necrosis, severe cellulitis, thrombophlebitis, or painful induration; usually accompanied by immediate burning sensation at injection site.^{125 215}

Liposomal daunorubicin citrate: Injection site inflammation reported rarely; tissue necrosis associated with extravasation not reported to date.¹³³ If extravasation occurs, aspirate as much infiltrated drug as possible; ^f may minimize local reaction by promptly infiltrating area with hydrocortisone sodium succinate injection (50–100 mg hydrocortisone) and/or sodium bicarbonate (5 mL of 8.4% injection) and applying cold compresses.^{165 206}

Infusion-related Effects

Liposomal daunorubicin citrate: Triad of back pain, flushing, and chest tightness reported in about 14% of patients in clinical trials; generally occurs during first 5 minutes of infusion, subsides with infusion interruption, and generally does not recur if infusion resumed at slower rate.¹³³ Symptoms appear to be related to lipid component since also reported with other liposomal preparations.¹³³

Carcinogenicity

Secondary leukemias reported in patients exposed to topoisomerase II inhibitors when used concomitantly with other antineoplastic agents or radiation therapy.^{125 215}

Sensitivity Reactions

Dermatologic Reactions

Conventional daunorubicin hydrochloride: Rash, contact dermatitis, urticaria reported rarely.²¹⁵

Hypersensitivity Reactions

Conventional daunorubicin hydrochloride: Anaphylactoid reactions reported rarely.²¹⁵

Liposomal daunorubicin citrate: Allergic reactions and pruritus reported.¹³³

General Precautions

Adequate Patient Evaluation and Monitoring

Administer only under the supervision of a qualified clinician experienced in the use of cancer chemotherapy agents.^{133 215}

Closely observe patient and frequently determine CBC; evaluate cardiac, renal, and hepatic function prior to each course of treatment.^{125 133 215}

Take appropriate measures to control systemic infections before beginning therapy;^{125 215} however, in some patients with acute leukemia, treatment of underlying malignancy in addition to other therapy (e.g., antibiotics) may be necessary before systemic infections can be controlled.^f

Hyperuricemia

Conventional daunorubicin hydrochloride: Possible hyperuricemia secondary to extensive purine catabolism accompanying rapid cellular destruction; monitor serum uric acid concentrations.^{125 215} Minimize or prevent by administering allopurinol prior to initiation of antileukemic therapy.^{125 215}

Specific Populations

Pregnancy

Category D.^{133 215} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether daunorubicin is distributed into human milk.^{125 215} Discontinue nursing because of potential risk to nursing infants.^{125 215}

Pediatric Use

Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with adults.^{125 215}

Liposomal daunorubicin citrate: Safety and efficacy not established.¹³³

Geriatric Use

Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with younger adults.^{125 215} Use with caution in patients with age-related bone marrow reserve inadequacies; consider dosage adjustment in patients with age-related renal impairment.^{125 215}

Liposomal daunorubicin citrate: Safety and efficacy not established.¹³³

Hepatic Impairment

Possible enhanced toxicity; dosage adjustment recommended.^{125 133 215} (See Hepatic Impairment under Dosage and Administration.)

Limited clinical experience with liposomal daunorubicin citrate in patients with hepatic impairment; reduce dosage based on experience with conventional daunorubicin.²¹⁵

Renal Impairment

Possible enhanced toxicity; dosage adjustment recommended.^{125 133 215} (See Renal Impairment under Dosage and Administration.)

Limited clinical experience with liposomal daunorubicin citrate in patients with renal impairment; reduce dosage based on experience with conventional daunorubicin.¹³³

Common Adverse Effects

Conventional daunorubicin hydrochloride: Alopecia, nausea/vomiting, myelosuppression, mucositis.²¹⁵

Liposomal daunorubicin citrate: Myelosuppression, opportunistic infections, infusion-related effects (back pain, flushing, chest tightness), neuropathy, nausea, vomiting, alopecia, fever, fatigue.¹³³

No formal drug interaction studies conducted with liposomal daunorubicin, but interactions not observed when administered concomitantly with various antiretroviral, antiviral, or anti-infective agents.¹³³

Myelosuppressive Agents

Potential pharmacodynamic interaction (additive myelosuppressive effects); dosage reduction of daunorubicin may be required.^{125 215}

Hepatotoxic Agents

Possible impairment of hepatic function and increased risk of toxicity.^{125 215}

Specific Drugs

DAUNOrubicin Pharmacokinetics

Encapsulation in liposomes substantially alters pharmacokinetics relative to conventional IV formulations (i.e., nonencapsulated drug).¹³³

Absorption

Bioavailability

Peak plasma daunorubicin concentrations following IV administration of liposomal daunorubicin citrate are higher than those following IV administration of conventional daunorubicin hydrochloride.¹⁶⁴

Distribution

Extent

Conventional daunorubicin hydrochloride: Rapidly and widely distributed into tissues, with highest concentrations in the spleen, kidneys, liver, lungs, and heart; absorbed by cells and binds to cellular components, particularly nucleic acids.^{125 215} Does not appear to cross blood-brain barrier.^{125 215}

Appears to cross placenta, but not known whether distributed into milk.^{125 215}

Liposomal daunorubicin citrate: Does not distribute into plasma and tissues as widely as conventional daunorubicin hydrochloride; decreased distribution into peripheral compartment and increased distribution into Kaposi’s lesions compared with conventional IV formulation.¹³³ Distributes into Kaposi’s sarcoma lesions to a greater extent than into healthy skin.^{164 167} Appears to cross blood-brain barrier in animals; not known whether crosses blood-brain barrier in humans.¹³³

Plasma Protein Binding

Conventional daunorubicin hydrochloride: Approximately 63% (mainly albumin).¹⁶⁴

Liposomal daunorubicin citrate: Minimal.¹⁶⁴

Elimination

Metabolism

Conventional daunorubicin hydrochloride: Extensively metabolized in the liver and other tissues, mainly by cytoplasmic aldoketoreductases; daunorubicinol, the major metabolite, exhibits antineoplastic activity.^{125 164}

Liposomal daunorubicin citrate: Daunorubicinol metabolite detected only in low concentrations in plasma after IV administration.^{133 164 167 168}

Elimination Route

Conventional daunorubicin hydrochloride: Excreted in urine (14–25%) and bile (40%) as daunorubicin and its metabolites.^{125 215}

Half-life

Conventional daunorubicin hydrochloride: Triphasic for daunorubicin and metabolites.^f Daunorubicin elimination is biphasic: 45 minutes (initial phase) and 18.5 hours (terminal phase).¹²⁵ Daunorubicinol: terminal plasma half-life averages 26.7 hours.^{125 133 164 171}

Liposomal daunorubicin citrate: 4.4 hours (probably represents distribution half-life).^{133 164}

Special Populations

Liposomal daunorubicin citrate: Pharmacokinetics not evaluated in women, in different ethnic groups, or in patients with renal or hepatic impairment.¹³³

Stability

Storage

Parenteral

Powder for Injection (Conventional Daunorubicin Hydrochloride)

15–30°C.¹²⁵ Protect from light; store in carton until time of use.¹²⁵

Reconstituted solution is stable for 24 hours at room temperature and 48 hours under refrigeration; protect from exposure to sunlight.¹²⁵

Injection (Conventional Daunorubicin Hydrochloride)

2–8°C.²¹⁵ Protect from light; store in carton until time of use.²¹⁵

Prepared solution for infusion stable for 24 hours at 15–30°C; discard unused portion.²¹⁵

Liposomal Injection (Liposomal Daunorubicin Citrate)

2–8°C.¹³³ Protect from light; do not freeze.¹³³

When diluted as directed with dextrose 5% injection, solution is stable for up to 6 hours at 2–8°C.¹³³

Compatibility

Parenteral

Conventional Daunorubicin Hydrochloride

The manufacturers recommend that no other drugs be mixed with conventional daunorubicin hydrochloride.²¹⁵

Solution Compatibility (Conventional Daunorubicin Hydrochloride)215 HID

Drug Compatibility

Liposomal Daunorubicin Citrate

The manufacturer states that liposomal daunorubicin citrate may be mixed only with dextrose 5% injection; must not be mixed with saline, bacteriostatic agents (e.g., benzyl alcohol), or any other solution.¹³³

Actions

• Exhibits antimitotic and cytotoxic activity.¹²⁵ Intercalates into DNA and inhibits topoisomerase II (by stabilizing the complex between this enzyme and DNA), resulting in single-strand and double-strand breaks in DNA.¹²⁵

• Also may inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.^{215 f}

• Also has antibacterial and immunosuppressive properties.^f

Advice to Patients

• Risk of myelosuppression; importance of informing clinicians if fever, sore throat, or unusual bleeding or bruising occurs.^{215 f}

• Risk of cardiotoxicity; advise patients of need for regular cardiac monitoring during and after therapy.^{133 215}

• Importance of patients informing clinicians immediately if any stinging or burning at IV injection site occurs during administration.^f

• Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy.^{133 215}

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.^{133 215}

• Probable alopecia; possible transient red coloration of urine after initiation of conventional (nonencapsulated) daunorubicin hydrochloride.^{125 215}

• Importance of informing patients of other important precautionary information.^{133 215} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• What drugs are contained in Vyxeos?

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