|Manufacturer:||Gilead Sciences, Inc.|
|Other Info:||Gilead Sciences, Inc.650 Cliffside Drive • San Dimas, CA 91773 USAFor medical information about DaunoXome (daw-nuh-zome), call 800-GILEAD-5 (800-445-3235).DaunoXome is a registered trademark of Gilead Sciences, Inc.Copyright 1996, Gilead Sciences, Inc.All rights reserved.Rev.7/0283030119906|
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.
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)