DAUNORUBICIN HYDROCHLORIDE 
■ DAUNORUBICIN CITRATE LIPOSOMAL INJECTION
Pronounciation
Trade Name(s)
- (daw-noh-ROO-bih-sin SIH-trate LIP-oh-sohm-ul)
DAUNORUBICIN HYDROCHLORIDE
■ DAUNORUBICIN CITRATE LIPOSOMAL INJECTION
Pronounciation
Trade Name(s)
Verify pregnancy status. Baseline studies indicated; see Monitor.
Adult acute nonlymphocytic leukemia:
45 mg/M2/day on Days 1, 2, and 3 in adults under age 60 (adults over age 60 may require reduction to 30 mg/M2/day). Used in specific protocol combination therapy (e.g., cytarabine 100 mg/M2/day for 7 days). Regimen repeated every 3 to 4 weeks. In these subsequent courses, repeat daunorubicin, 30 to 45 mg/M2/day (depending on age) for only 2 days and cytarabine for only 5 days. To obtain a normal-appearing bone marrow may require up to 3 courses.
Adult acute lymphocytic leukemia:
45 mg/M2/day on Days 1, 2, and 3. Used in combination therapy (e.g., vincristine, prednisone, and L-asparaginase). In all situations, when remission is complete, an individual maintenance program should be established.
DaunoXome (Liposomal Injection)
Advanced, HIV-associated Kaposi’s sarcoma:
40 mg/M2 as an IV infusion. Repeat every 2 weeks. Continue treatment until there is evidence of disease progression (specifics outlined in package insert).
See Maternal/Child.
Acute lymphocytic leukemia in pediatric patients 2 years of age and older:
25 mg/M2/day on Day 1 each week, vincristine 1.5 mg/M2 on Day 1 each week, and prednisone 40 mg/M2 PO daily. Remission should be obtained in 4 weeks. If a partial remission is obtained after 4 weeks, 1 or 2 more weeks of treatment may produce a complete remission.
Acute lymphocytic leukemia in infants and children under 2 years of age or less than 0.5 M2 body surface:
Calculate dose based on weight instead of body surface area: 1 mg/kg.
Safety for use in pediatric patients not established.
See Precautions/Monitor.
Profound bone marrow suppression is usually required to eradicate the leukemic cells and induce a complete remission. Evaluate bone marrow and peripheral blood to determine need for additional courses.
■ See Usual Dose for adults over 60 years of age.
■ Reduce dose in impaired hepatic or renal function according to the following chart.
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Reduce dose to 75% of normal (30 mg/M2) if serum bilirubin is 1.2 to 3 mg/dL. Reduce dose to 50% of normal (20 mg/M2) if serum bilirubin or creatinine is greater than 3 mg/dL.
■ Withhold dose if absolute granulocyte count is less than 750 cells/mm3.
seePrecautions.
Each 20 mg must be diluted with 4 mL of SWFI (5 mg/mL). Agitate gently to dissolve completely. Further dilute each dose with 10 to 15 mL of NS. Must be given through Y-tube of a free-flowing infusion of D5W or NS. May be added to 100 mL NS and given as an infusion. Use extreme caution.
Dilute each single dose with an equal amount of D5W. Available as a 2 mg/mL preservative-free solution. Withdraw calculated volume (dose of DaunoXome) from vial; transfer to a sterile infusion bag that contains an equal volume of D5W. Desired concentration is 1 mg/mL. Do not use any other diluent. A translucent red liposomal dispersion; do not use if opaque. Do not use in-line filters for infusion. See Compatibility.
Manufacturer states, “Do not use in-line filters for infusion.”
Protect from sunlight. Diluted solution stable 24 hours at room temperature, 48 hours if refrigerated; then discard.
Refrigerate unopened vials; avoid freezing. Protect from light. Discard unused drug. Reconstituted solutions may be refrigerated for a maximum of 6 hours.
Manufacturer states, “Should not be administered mixed with other drugs or heparin.”
Other sources suggest a few specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Manufacturer states, “The only fluid that may be mixed with DaunoXome is D5W. Must not be mixed with saline, bacteriostatic agents such as benzyl alcohol, or any other solution.”
A single dose of properly diluted medication over 3 to 5 minutes.
A single dose evenly distributed over 30 to 45 minutes.
A single dose as an infusion evenly distributed over 60 minutes. Do not use an in-line filter. Back pain, flushing, and chest tightness may occur. Usually subsides if infusion is stopped and usually does not recur if infusion is restarted at a slower rate after symptoms subside.
A highly toxic antibiotic antineoplastic agent. Rapidly cleared from plasma, it inhibits synthesis of DNA. Cell-cycle specific for S phase; exact method of action is unknown; antimitotic, cytotoxic, and immunosuppressive. Widely distributed in tissues, with the highest concentrations occurring in the spleen, kidneys, liver, lungs, and heart. Does not cross blood-brain barrier. Metabolized in the liver and other tissues. Elimination half-life is 18 to 30 hours. Slowly excreted in bile and urine.
A liposomal preparation of daunorubicin formulated to maximize selectivity for solid tumors. In the circulation, the liposomal preparation protects the entrapped daunorubicin from chemical and enzymatic degradation, minimizes protein binding, and generally decreases uptake by normal (non–reticuloendothelial system) tissues. The mechanism of delivery is not known, but may be through the often altered and/or compromised vasculature of tumors. In animals, it has been shown to accumulate in tumors to a greater extent than conventional daunorubicin. Released over time within the cells of the solid tumor. Persists at high levels within tumor tissue for several days. It differs from conventional daunorubicin because it mostly confines itself to vascular fluid volume. Plasma clearance is slower and the AUC (area under the curve) is larger.
Treatment of acute nonlymphocytic leukemia in adults (myelogenous, monocytic, erythroid).
■ Combination therapy for induction of remission in acute lymphocytic leukemia in adults and pediatric patients.
Currently approved only for first-line cytotoxic therapy for advanced HIV-associated Kaposi’s sarcoma.
Hypersensitivity to daunorubicin or any of its components. Not absolute: Pre-existing bone marrow suppression, impaired cardiac function, pre-existing infection; see Precautions.
History of hypersensitivity reaction to previous treatment with DaunoXome or any of its components (includes conventional daunorubicin). Not recommended in patients with less than advanced HIV-related Kaposi’s sarcoma.
Follow guidelines for handling cytotoxic agents. See Appendix A, p. 1308.
■ Administered by or under the direction of the physician specialist with facilities for monitoring the patient and responding to any medical emergency.
■ For IV use only; do not give IM or SQ.
■ Severe myelosuppression may occur and may lead to infection or hemorrhage.
■ Use extreme caution in pre-existing drug-induced bone marrow suppression, existing heart disease, previous treatment with other anthracyclines (e.g., doxorubicin), or radiation therapy encompassing the heart.
■ Incidence of myocardial toxicity increases after a total cumulative dose that exceeds 400 to 550 mg/M2 in adults, 300 mg/M2 in pediatric patients over 2 years of age, or 10 mg/kg in pediatric patients under 2 years of age. Potentially fatal congestive heart failure may occur either during therapy or months to years after therapy is complete.
■ Urine may be reddish color (from dye, not hematuria).
Monitor CBC including differential and platelet count before each dose.
■ Monitoring of liver function, kidney function, ECG, chest x-ray, echocardiography, and systolic ejection fraction indicated before and during therapy; recommended before each course.
■ Evaluation of cardiac function by medical history and physical exam is recommended before each dose; see Precautions.
■ Monitor closely for S/S of hemorrhage or infection; may be life threatening.
■ Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient.
■ Determine absolute patency of vein. A stinging or burning sensation indicates extravasation; discontinue injection and use another vein. Severe cellulitis and tissue necrosis will result from extravasation with conventional daunorubicins; has not been observed with DaunoXome.
■ Prophylactic antiemetics may reduce nausea and vomiting and increase patient comfort.
■ Monitor uric acid levels; maintain hydration; uric acid–lowering drugs (e.g., allopurinol) may be indicated.
■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood).
May cause acute congestive heart failure with total cumulative doses over 550 mg/M2 in adults (400 mg/M2 if previous treatment with doxorubicin or radiation therapy in area of heart), 300 mg/M2 in pediatric patients over 2 years of age, and 10 mg/kg in pediatric patients under 2 years of age.
May also cause cardiomyopathy. Monitoring of LVEF recommended at total cumulative doses of 320 mg/M2, 480 mg/M2, and every 240 mg/M2 thereafter.
Effective birth control recommended.
■ Report IV site burning or stinging promptly.
■ Secondary leukemias have been reported.
■ See Appendix D, p. 1311.
Category D: can cause fetal harm. Avoid pregnancy.
■ Safety for use in breast-feeding not established; discontinue breast-feeding.
■ Cardiotoxicity may be more frequent and occur at lower cumulative doses in pediatric patients.
■ See Monitor.
Safety for use in pediatric patients not established.
Cardiotoxicity and myelotoxicity may be more severe. Consider age-related renal impairment. Safety of DaunoXome for use in the elderly has not been established.
Concurrent use with cyclophosphamide may increase cardiotoxicity.
■ Dose reduction may be required with concurrent use of other myelosuppressive agents.
■ Concurrent use with hepatotoxic agents (e.g., high-dose methotrexate) may increase risk of toxicity.
■ Risk of cardiotoxicity increased in patients previously treated with maximum cumulative doses of other anthracyclines (e.g., doxorubicin, idarubicin) and/or radiation encompassing the heart.
■ Do not administer vaccines or chloroquine to patients receiving antineoplastic drugs.
■ See Precautions.
Bone marrow suppression and cardiotoxicity are dose related and dose limiting.
Acute congestive heart failure, alopecia (reversible), bone marrow suppression (marked with average doses), chills, decrease in systolic ejection fraction, depressed QRS voltage, diarrhea, fever, gonadal suppression, mucositis, myocarditis, nausea, pericarditis, skin rash, vomiting.
Granulocytopenia is most common. Symptoms common to conventional daunorubicin may also occur. Infusion-related back pain, chest tightness, and flushing may be related to liposomal formulation.
Will cause increased severity of myelosuppression, fatigue, nausea, and vomiting.
Most side effects will be tolerated or treated symptomatically. Keep physician informed. Close monitoring of cumulative dosage, bone marrow, ECG, chest x-ray, echocardiography, and systolic ejection fraction may prevent most serious and potentially fatal side effects. There is no specific antidote. Supportive therapy as indicated will help sustain the patient in toxicity. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim, sargramostim) may be indicated to treat bone marrow toxicity. For extravasation, aspirate as much infiltrated drug as possible, flood site with normal saline, and inject hydrocortisone sodium succinate or hyaluronidase throughout extravasated tissue. Use a 27- or 25-gauge needle. Cold, moist compresses may be helpful; elevate extremity. Site should be observed promptly by a reconstructive surgeon.