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daunorubicin citrate

Class: Antineoplastic Agents
Note: This monograph also contains information on daunorubicin hydrochloride
VA Class: AN200
CAS Number: 23541-50-6
Brands: Cerubidine, DaunoXome

Warning(s)

  • Extravasation
  • Severe local tissue necrosis if extravasation occurs.133 215 Do not administer IM or sub-Q.125 215 (See Local Effects under Cautions.)

  • Myocardial Toxicity
  • Possible cardiotoxicity and potentially fatal CHF during or months to years after therapy;133 215 increased risk with cumulative dosages >400–550 mg/m2 in adults, >300 mg/m2 in children >2 years of age, or >10 mg/kg in children <2 years of age.215 (See Cardiotoxicity under Cautions.)

  • Monitor cardiac function regularly, especially in patients with pre-existing cardiac disease or those who have received prior anthracyclines or have had prior radiotherapy encompassing the heart.133

  • Myelosuppression
  • Severe myelosuppression may occur,125 133 215 possibly resulting in infection or hemorrhage.125 215 (See Hematologic Effects under Cautions.)

  • Hepatic and Renal Impairment
  • Reduce dosage in patients with hepatic or renal impairment.125 133 215 (See Special Populations under Dosage and Administration.)

  • Experience of Supervising Clinician
  • Administer only under the supervision of a qualified clinician experienced in the use of antineoplastic agents.125 133 215 Use only when adequate treatment facilities for appropriate management of therapy and complications are available.125 215

  • Infusion-related Effects
  • Triad of back pain, flushing, and chest tightness reported in patients receiving liposomal daunorubicin citrate; generally occurs during first 5 minutes of infusion, subsides with infusion interruption, and generally does not recur if infusion resumed at slower rate.133 (See Infusion-related Effects under Cautions.)

Introduction

Antineoplastic agent; anthracycline glycoside antibiotic.133 127

Uses for daunorubicin citrate

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

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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 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.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 citrate Dosage and Administration

General

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

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 citrate

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

Interactions for daunorubicin citrate

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

Drug

Interaction

Comments

Cyclophosphamide

Possible increased cardiotoxicity with concurrent use125 215

Doxorubicin

Increased risk of cardiotoxicity if daunorubicin used in a patient previously treated with doxorubicin125 215

Do not use daunorubicin in patients who have previously received maximum recommended cumulative doses of doxorubicin or daunorubicin125 215

Methotrexate

Possible hepatic impairment and increased risk of toxicity125 215

daunorubicin citrate 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

For information on systemic interactions resulting from concomitant use, see Interactions.

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

Compatible

Dextrose 3.3% in sodium chloride 0.3%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture Compatibility (Conventional Daunorubicin Hydrochloride)215fHID

Compatible

Cytarabine with etoposide

Hydrocortisone sodium succinate

Incompatible

Dexamethasone sodium phosphate

Heparin sodium

Y-site Compatibility (Conventional Daunorubicin Hydrochloride)215HID

Compatible

Amifostine

Anidulafungin

Caspofungin acetate

Etoposide phosphate

Filgrastim

Gemcitabine HCl

Granisetron HCl

Melphalan HCl

Methotrexate sodium

Ondansetron HCl

Sodium bicarbonate

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Aztreonam

Fludarabine phosphate

Piperacillin sodium–tazobactam sodium

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.

Daunorubicin Citrate Liposomal

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

2 mg (of daunorubicin) per mL (50 mg)

DaunoXome

Gilead

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

Daunorubicin Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

20 mg (of daunorubicin)

Cerubidine

Bedford

Injection

5 mg (of daunorubicin) per mL*

Daunorubicin Hydrochloride Injection

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 20, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

125. Bedford Laboratories. Cerubidine (daunorubicin hydrochloride) for injection prescribing information. Bedford, OH; 2004 Jun.

126. Gottlieb AJ, Weinberg V, Ellison RR et al. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984; 64:267-74. [IDIS 187984] [PubMed 6375760]

127. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

128. Childhood acute lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2012 May 18.

129. Adult acute lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2012 May 10.

130. Margolin JF, Rabin KR, Poplack DG. Leukemias and lymphomas of childhood. In: DeVita VT Jr, Lawrence TS, Rosenberg SA et al, eds. DeVita, Hellman, and Rosenberg's cancer: principles and practice of oncology. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.

131. Preti A, Kantarjian HM. Management of adult acute lymphocytic leukemia: present issues and key challenges. J Clin Oncol. 1994; 12:1312-22. [IDIS 331854] [PubMed 8201394]

132. Kebriaei P, Champlin R, De Lima M et al. Management of acute leukemias. In: DeVita VT Jr, Lawrence TS, Rosenberg SA et al, eds. DeVita, Hellman, and Rosenberg's cancer: principles and practice of oncology. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.

133. Gilead Sciences. DaunoXome (daunorubicin citrate liposome injection) prescribing information. San Dimas, CA; 2002 Jul.

134. Presant CA, Scolaro M, Kennedy P et al. Liposomal daunorubicin treatment of HIV-associated Kaposi’s sarcoma. Lancet. 1993; 341:1242-3. [IDIS 314333] [PubMed 8098393]

135. Gill PS, Wernz J, Scadden DT et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Onco. 1996; 14:2353-64.

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