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Black Box Warning
WARNINGS
See full prescribing information for complete Boxed Warning.
* Cardiac function should be monitored regularly in patients receiving DaunoXome (daunorubicin citrate liposome injection) because of the potential risk for cardiac toxicity and congestive heart failure. Cardiac monitoring is advised especially in those patients who have received prior anthracyclines or who have pre-existing cardiac disease or who have had prior radiotherapy encompassing the heart.
Severe myelosuppression may occur.
DaunoXome should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
Dosage should be reduced in patients with impaired hepatic function.
A triad of back pain, flushing, and chest tightness has been reported in 13.8% of the patients (16/116) treated with DaunoXome in the Phase III clinical trial, and in 2.7% of treatment cycles (27/994). This triad generally occurs during the first five minutes of the infusion, subsides with interruption of the infusion, and generally does not recur if the infusion is then resumed at a slower rate.
Overview
Daunorubicin liposome is an anthracycline that is FDA approved for the treatment of advanced HIV-associated Kaposi's sarcoma. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Cardiotoxicity, Myelosuppression.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Colon cancer
In a phase II clinical trial, DAUNOrubicin citrate liposome in doses of 100 milligrams/square meter every 3 weeks was not associated with significant antitumor activity in patients with metastatic ADENOCARCINOMA OF THE COLON progressing after 5-fluorouracil
Do not mix DaunoXome with other drugs.
Kaposi's sarcoma, First line therapy; in patients with advanced HIV-related Kaposi's sarcoma
Important note: The dose OF Daunorubicin citrate liposome is different than that of conventional Daunorubicin and the two formulations are not interchangeable. Consult the drug evaluation monograph entitled "daunorubicin" for clinical use of this formulation.
Daunorubicin citrate liposome is indicated as a first-line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma. It is not recommended in patients with less than advanced Kaposi's sarcoma. The dose of DAUNOrubicin citrate liposome is 40 milligrams/square meter, administered intravenously over 60 minutes, every 2 weeks. Blood counts should be repeated prior to each dose, and therapy withheld if the absolute granulocyte count is less than 750 cells/cubic millimeter. Treatment should be continued until there is evidence of progressive disease (eg, based on best response achieved: new visceral sites of involvement, or progression of visceral disease; development of 10 or more new cutaneous lesions or a 25% increase in the number of lesions compared to baseline; a change in the character of 25% or more of all previously counted flat lesions to raised; increase in the surface area the indicator lesions), or until other complications of HIV disease require discontinuation of therapy.
In the treatment of AIDS-related Kaposi's sarcoma, the recommended dose of DAUNOrubicin citrate liposome is 40 milligrams/square meter every 14 days. The median duration of response in one study was 12 weeks.
Important Note: The dose of DAUNOrubicin CITRATE LIPOSOME is different than that of conventional DAUNOrubicin and the two formulations are not interchangeable. Consult the Drug Evaluation monograph entitled "DAUNOrubicin" for clinical use of this formulation.
Infiltration: Care should be given to avoid extravasation.
Intravenous rate of administration: DAUNOrubicin citrate liposome should be administered diluted in 5% Dextrose in Water for Injection in volumes of 100 mL and administered via intravenous infusion over 60 minutes. The manufacturer of DAUNOrubicin citrate liposome emphasizes that an inline filter should NOT be used.
Intravenous solution preparation
DAUNOrubicin citrate liposome should be diluted 1:1 with 5% Dextrose Injection (D5W) before administration. Each vial of DaunoXome(R) contains DAUNOrubicin citrate equivalent to 50 milligrams DAUNOrubicin base, at a concentration of 2 mg/mL. The recommended concentration after dilution is 1 mg/mL. The only fluid which may be mixed with DaunoXome(R) is 5% Dextrose Injection; the drug must not be mixed with saline, bacteriostatic agents such as benzyl alcohol, or any other solution. Strictly observe aseptic technique in all handling. Do not use an inline filter for intravenous infusion of DaunoXome.
The calculated volume of DAUNOrubicin citrate liposome should be drawn from the vial into a sterile syringe, and transferred into a sterile infusion bag containing an equivalent volume of 5% Dextrose Injection (D5W). Diluted DAUNOrubicin citrate liposome should be administered immediately; if not used immediately, the dose should be stored refrigerated at 2 to 8 degrees Centigrade (36 to 46 degrees Fahrenheit) for a maximum of 6 hours.
Dosage in Renal Failure
There is limited clinical experience in treating patients with renal impairment with DAUNOrubicin citrate liposome. Thus, based on experience with conventional DAUNOrubicin hydrochloride, it is recommended that the dose of DAUNOrubicin citrate liposome be reduced if the serum creatinine is elevated as follows: For serum creatinine greater than 3 mg/dL, give one-half the normal dose.
Dosage in Hepatic Insufficiency
There is limited clinical experience in treating patients with hepatic impairment with DAUNOrubicin citrate liposome. Thus, based on experience with DAUNOrubicin hydrochloride, it is recommended that the dose of DAUNOrubicin citrate liposome be reduced if the serum bilirubin is elevated as follows: For serum bilirubin 1.2 to 3 milligrams/deciliter, give three-fourths the normal dose; for serum bilirubin greater than 3 mg/dL, give one-half the normal dose.
Geriatric Use
The safety and efficacy of DAUNOrubicin citrate liposome in the elderly have not been established
There is limited information regarding Off-Label Guideline-Supported Use of Daunorubicin liposome in adult patients.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Daunorubicin liposome in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Daunorubicin liposome in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness in pediatric patients have not been established.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Daunorubicin liposome in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Daunorubicin liposome in pediatric patients.
Contraindications
Therapy with DaunoXome is contraindicated in patients who have experienced a serious hypersensitivity reaction to previous doses of DaunoXome or to any of its constituents.
Warnings
Precautions
DaunoXome is intended for administration under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
The primary toxicity of DaunoXome is myelosuppression, especially of the granulocytic series, which may be severe, and associated with fever and may result in infection. Effects on the platelets and erythroid series are much less marked. Careful hematologic monitoring is required and since patients with HIV infection are immunocompromised, patients must be observed carefully for evidence of intercurrent or opportunistic infections.
Special attention must be given to the potential cardiac toxicity of DaunoXome. Although there is no reliable means of predicting congestive heart failure, cardiomyopathy induced by anthracyclines is usually associated with a decrease of the left ventricular ejection fraction (LVEF). Cardiac function should be evaluated in each patient by means of a history and physical examination before each course of DaunoXome and determination of LVEF should be performed at total cumulative doses of DaunoXome of 320 mg/m2, and every 160 mg/m2 thereafter.
Patients who have received prior therapy with anthracyclines (doxorubicin > 300 mg/m2 or equivalent), have pre-existing cardiac disease, or have received previous radiotherapy encompassing the heart may be less "cardiac" tolerant to treatment with DaunoXome. Therefore, monitoring of LVEF at cumulative DaunoXome doses should occur prior to therapy and every 160 mg/m2 of DaunoXome.
In patients with Kaposi's sarcoma, congestive heart failure has been reported in one patient at a cumulative dose of 340 mg/m2 of DaunoXome. In eight Kaposi's sarcoma patients, LVEF decreases were reported at cumulative doses ranging from 200 mg/m2 to 2100 mg/m2 (median dose 320 mg/m2) of DaunoXome. In clinical studies in malignancies other than Kaposi's sarcoma and treated with doses of DaunoXome greater than the recommended dose of 40 mg/m2, congestive heart failure has been reported at a cumulative dose as low as 200 mg/m2 of DaunoXome; seven patients have been reported with LVEF decreases. The proportion of patients at risk for cardiotoxicity is unknown because the denominator is uncertain since there were several instances of missing repeat cardiac evaluations.
A triad of back pain, flushing, and chest tightness has been reported in 13.8% of the patients (16/116) treated with DaunoXome in the randomized clinical trial and in 2.7% of treatment cycles (27/994). This triad generally occurs during the first five minutes of the infusion, subsides with interruption of the infusion, and generally does not recur if the infusion is then resumed at a slower rate. This combination of symptoms appears to be related to the lipid component of DaunoXome, as a similar set of signs and symptoms has been observed with other liposomal products not containing daunorubicin.
Daunorubicin has been associated with local tissue necrosis at the site of drug extravasation. Although no such local tissue necrosis has been observed with DaunoXome, care should be taken to ensure that there is no extravasation of drug when DaunoXome is administered.
Dosage should be reduced in patients with impaired hepatic function
Adverse Reactions
Clinical Trials Experience
DaunoXome contains daunorubicin, encapsulated within a liposome. Conventional daunorubicin has acute myelosuppression as its dose limiting side effect, with the greatest effect on the granulocytic series. In addition, daunorubicin causes alopecia, and nausea and vomiting in a significant number of patients treated. Extravasation of conventional daunorubicin can cause severe local tissue necrosis. Chronic therapy at total doses above 300 mg/m2 causes a cumulative-dose-related cardiomyopathy with congestive heart failure.
Administered as DaunoXome, daunorubicin has substantially altered pharmacokinetics and some differences in toxicity. The most important acute toxicity of DaunoXome remains myelosuppression, principally of the granulocytic series, with much less marked effects on the platelets and erythroid series.
In an open-label, randomized, controlled clinical trial conducted in 13 centers in the U.S.A. and Canada in advanced HIV-related Kaposi's sarcoma, two treatment regimens were compared as first line cytotoxic therapy: DaunoXome and ABV (doxorubicin (Adriamycin®), bleomycin, and vincristine). All drugs were administered intravenously every 2 weeks. The safety data presented below include all reported or observed adverse experiences, including those not considered to be drug related. Patients with advanced HIV-associated Kaposi's sarcoma are seriously ill due to their underlying infection and are receiving several concomitant medications including potentially toxic antiviral and antiretroviral agents. The contribution of the study drugs to the adverse experience profile is therefore difficult to establish.
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Daunorubicin liposome in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
Drug
Description
Use in Specific Populations
Pregnancy
Pregnancy Category
Labor and Delivery
There is no FDA guidance on use of Daunorubicin liposome during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Daunorubicin liposome with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Daunorubicin liposome with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Daunorubicin liposome with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Daunorubicin liposome with respect to specific gender populations.
Race
There is no FDA guidance on the use of Daunorubicin liposome with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Daunorubicin liposome in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Daunorubicin liposome in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Daunorubicin liposome in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Daunorubicin liposome in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
There is limited information regarding Monitoring of Daunorubicin liposome in the drug label.
Description
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Daunorubicin liposome in the drug label.
