Daunoxome
Loading...Daunoxome Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
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. (See DOSAGE AND ADMINISTRATION)
Pregnancy Category D
DaunoXome can cause fetal harm when administered to a pregnant woman. DaunoXome was administered to rats on gestation days 6 through 15 at 0.3, 1.0 or 2.0 mg/kg/day, (about 1/20th, 1/6th, or 1/3rd the recommended human dose on a mg/m2 basis). DaunoXome produced severe maternal toxicity and embryolethality at 2.0 mg/kg/day and was embryotoxic and caused fetal malformations (anophthalmia, microphthalmia, incomplete ossification) at 0.3 mg/kg/day. Embryotoxicity was characterized by increased embryo-fetal deaths, reduced numbers of litters, and reduced litter sizes.
There are no studies of DaunoXome in pregnant women. If DaunoXome is used during pregnancy, or if the patient becomes pregnant while taking DaunoXome, the patient must be warned of the potential hazard to the fetus. Patients should be advised to avoid becoming pregnant while taking DaunoXome.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
DaunoXome is indicated as a first line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma. DaunoXome is not recommended in patients with less than advanced HIV-related Kaposi's sarcoma.
History
There is currently no drug history available for this drug.
Other Information
DaunoXome (daunorubicin citrate liposome injection) is a sterile, pyrogen-free, preservative-free product in a single use vial for intravenous infusion.
DaunoXome contains an aqueous solution of the citrate salt of daunorubicin encapsulated within lipid vesicles (liposomes) composed of a lipid bilayer of distearoylphosphatidylcholine and cholesterol (2:1 molar ratio), with a mean diameter of about 45 nm. The lipid to drug weight ratio is 18.7:1 (total lipid:daunorubicin base), equivalent to a 10:5:1 molar ratio of distearoylphosphatidylcholine:cholesterol:daunorubicin. Daunorubicin is an anthracycline antibiotic with antineoplastic activity, originally obtained from Streptomyces peucetius. Daunorubicin has a 4-ring anthracycline moiety linked by a glycosidic bond to daunosamine, an amino sugar. Daunorubicin may also be isolated from Streptomyces coeruleorubidus and has the following chemical name: (8S-cis)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione hydrochloride.
Daunorubicin citrate has the following chemical structure:
DSPC (distearoylphosphatidylcholine) has the following chemical structure:
The following represents the idealized, spherical morphology of a liposome:
Note: Liposomal encapsulation can substantially affect a drug's functional properties relative to those of the unencapsulated drug.
In addition, different liposomal drug products may vary from one another in the chemical composition and physical form of the liposomes. Such differences can substantially affect the functional properties of liposomal drug products.
Each vial contains daunorubicin citrate equivalent to 50 mg of daunorubicin base, encapsulated in liposomes consisting of 704 mg distearoylphosphatidylcholine and 168 mg cholesterol. The liposomes encapsulating daunorubicin are dispersed in an aqueous medium containing 2,125 mg sucrose, 94 mg glycine, and 7 mg calcium chloride dihydrate in a total volume of 25 mL/vial. The pH of the dispersion is between 4.9 and 6.0. The liposome dispersion should appear red and translucent.
Sources
Daunoxome Manufacturers
-
Galen Us Inc
![Daunoxome (Daunorubicin Citrate) Injection, Lipid Complex [Galen Us Inc]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Daunoxome | Galen Us Inc
DaunoXome should be administered intravenously over a 60 minute period at a dose of 40 mg/m2, with doses repeated every two weeks. Blood counts should be repeated prior to each dose, and therapy withheld if the absolute granulocyte count is less than 750 cells/mm3. Treatment should be continued until there is evidence of progressive disease (e.g., 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 surface area of the indicator lesions), or until other intercurrent complications of HIV disease preclude continuation of therapy.
Patients with Impaired Hepatic and Renal Function
Limited clinical experience exists in treating hepatically and renally impaired patients with DaunoXome.
Therefore, based on experience with daunorubicin HCl, it is recommended that the dosage of DaunoXome be reduced if the bilirubin or creatinine is elevated as follows: Serum bilirubin 1.2 to 3 mg/dL, give ¾ the normal dose; serum bilirubin or creatinine > 3 mg/dL, give ½ the normal dose.
Do not mix DaunoXome with other drugs.Preparation Of Solution
DaunoXome should be diluted 1:1 with 5% Dextrose Injection (D5W) before administration. Each vial of DaunoXome contains daunorubicin citrate equivalent to 50 mg daunorubicin base, at a concentration of 2 mg/mL. The recommended concentration after dilution is 1 mg daunorubicin/mL of solution.
Use aseptic technique.
Aseptic technique must be strictly observed in all handling, since no preservative or bacteriostatic agent is present in DaunoXome or in the materials recommended for dilution.
Withdraw the calculated volume of DaunoXome from the vial into a sterile syringe, and transfer it into a sterile infusion bag containing an equivalent amount of D5W. Administer diluted DaunoXome immediately. If not used immediately, diluted DaunoXome should be refrigerated at 2°– 8 °C (36°– 46°F) for a maximum of 6 hours.
Caution: The only fluid which may be mixed with DaunoXome is D5W; DaunoXome must not be mixed with saline, bacteriostatic agents such as benzyl alcohol, or any other solution.
Do not use an in-line filter for the intravenous infusion of DaunoXome.
All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. DaunoXome is a translucent dispersion of liposomes that scatters light to some degree. Do not use DaunoXome if it appears opaque, or has precipitate or foreign matter present.
Procedures for proper handling and disposal of anticancer drugs should be followed.1–8
Login To Your Free Account