No

Antineoplastic Agent, Antibiotic

Advanced HIV-associated Kaposi's sarcoma; first-line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma

D

Hypersensitivity to previous doses or any constituents of the product

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered.

Although grade 3-4 injection site inflammation has been reported in patients treated with the liposomal daunorubicin, no instances of local tissue necrosis were observed with extravasation. However, refer to daunorubicin monograph and avoid extravasation.

Reduce dosage in patients with impaired hepatic function. Hyperuricemia can be induced secondary to rapid lysis of leukemic cells. As a precaution, administer allopurinol prior to initiating antileukemic therapy.

>10%:

Central nervous system: Fatigue, headache

Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea, vomiting

Hematologic: Neutropenia

Neuromuscular & skeletal: Neuropathy

Respiratory: Cough, dyspnea, rhinitis

Miscellaneous: Infection

5% to 10%:

Cardiovascular: Hypertension, palpitations, syncope, tachycardia, chest pain, edema

Central nervous system: Depression, dizziness, insomnia, malaise

Dermatologic: Alopecia, pruritus

Endocrine & metabolic: Hot flashes

Gastrointestinal: Constipation, stomatitis, tenesmus

Neuromuscular & skeletal: Arthralgia, myalgia

Ocular: Abnormal vision

Respiratory: Sinusitis

Symptoms of acute overdose are increased severities of the observed dose-limiting toxicities of therapeutic doses, myelosuppression (especially granulocytopenia), fatigue, nausea, vomiting

Treatment is symptomatic

Incompatible with sodium bicarbonate and 5-FU, heparin, dexamethasone

Store intact vials under refrigeration (2°C to 8°C/36°F to 46°F). Reconstitute liposomal daunorubicin 1:1 with 5% dextrose injection before administration. Store reconstituted solution for a maximum of 6 hours. Do not freeze and protect from light. Do not use an in-line filter for intravenous infusion.

Liposomal daunorubicin contains an aqueous solution of the citrate salt of daunorubicin encapsulated with lipid vesicles (liposomes) composed of a lipid bilayer of distearoylphosphatidylcholine and cholesterol (2:1 molar ratio). This liposomal daunorubicin is formulated to maximum the selectivity of daunorubicin for solid tumors in situ; refer to Daunorubicin monograph.

Distribution: V_d: 6.4 L

Half-life: 4.4 hours

Elimination: Plasma clearance: 17.3 mL/minute

Adults: I.V.: 40 mg/m² over 1 hour; repeat every 2 weeks; continue treatment until there is evidence of progressive disease

• Serum bilirubin 1.2-3 mg/dL: 3/4 normal dose recommended
• Serum bilirubin >3 mg/dL; serum creatinine >3 mg/dL: 1/2 normal dose recommended

Observe patient closely and monitor chemical and laboratory tests extensively. Evaluate cardiac, renal, and hepatic function prior to each course of treatment. Repeat blood counts prior to each dose and withhold if the absolute granulocyte count is <750 cells/mm³. Monitor serum uric acid levels.

May produce myelosuppression; caution with clozapine and carbamazepine

None reported

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help); you may experience loss of hair (reversible); you will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Urine may turn red-brown (normal). Yogurt or buttermilk may help reduce diarrhea (if unresolved, contact prescriber for medication relief). Report fever, chills, unusual bruising or bleeding, signs of infection, excessive fatigue, yellowing of eyes or skin, darkening in color of urine (red/pink), abdominal pain or blood in stools, swelling of extremities, difficulty breathing, or unresolved diarrhea. Pregnancy/breast-feeding precautions: Do not get pregnant or cause a pregnancy (males) while taking this medication; use appropriate barrier contraceptive measures during and for 1 month following therapy. Breast-feeding is not recommended.

Injection: 2 mg/mL (equivalent to 50 mg daunorubicin base) (1 mL, 4 mL, 10 mL unit packs)

Eckardt JR, Campbell E, Burris HA, et al, "A Phase II Trial of DaunoXome®, Liposome-Encapsulated Daunorubicin, in Patients With Metastatic Adenocarcinoma of the Colon," Am J Clin Oncol, 1994, 17(6):498-501.

Gill PS, Espina BM, Muggia F, et al, "Phase I/II Clinical and Pharmacokinetic Evaluation of Liposomal Daunorubicin," J Clin Oncol, 1995, 13(4):996-1003.

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 Oncol, 1996, 14(8):2353-64.

Guaglianone P, Chan K, Dela Flor-Weiss E, et al, "Phase I and Pharmacologic Study of Liposomal Daunorubicin (DaunoXome®)," Invest New Drugs, 1994, 12(2):103-10.

Schurmann D, Dormann A, Grunewald T, et al, "Successful Treatment of AIDS-Related Pulmonary Kaposi's Sarcoma With Liposomal Daunorubicin," Eur Respir J, 1994, 7(4):824-5.