Daunorubicin Citrate Liposomal

Trade Names:DaunoXome- Solution for injection 2 mg/mL (equivalent to 50 mg daunorubicin base)

Pharmacology

Anthracycline antibiotic formulated to increase selectivity for solid tumors in situ.

Pharmacokinetics

Distribution

Vd is approximately 6.4 L. Distribution t _½ approximately 4.41 h.

Metabolism

Metabolized to daunorubicinol (active).

Elimination

The t _½ is 4.4 h. Plasma Cl approximately 17.3 mL/min.

Indications and Usage

Advanced HIV-associated Kaposi sarcoma.

Contraindications

Standard considerations.

Dosage and Administration

IV 40 mg/m ² /dose (of daunorubicin base) administered over 1 h every 2 wk. The dose of daunorubicin citrate liposomal is different from the dose of daunorubicin hydrochloride.

If serum bilirubin is 1.2 to 3 mg/dL, then give 75% of adjusted dose from prior course. If serum bilirubin is more than 3 mg/dL or serum creatinine is more than 3 mg/dL, then give 50% of adjusted dose from prior course.

General Advice

• For IV infusion only.
• Follow institutional procedures for handling, administration, and disposal of anticancer drugs.
• Injection must be diluted prior to administration. Dilute injection concentrate 1:1 with dextrose 5% injection. Resulting solution contains 1 mg daunorubicin/mL.
• Discard unused portions of vial. Do not save any unused portions for future use.
• Do not mix with any other IV solution than dextrose 5% nor mix with any other medication.
• Do not administer if solution is opaque or contains particulate matter. Solution will have a red discoloration and disperse light to some degree.
• Administer prescribed dose over a 60-min period into free-flowing IV, taking precautions to avoid extravasation. Do not use an in-line filter.

Storage/Stability

Store vials in refrigerator (36° to 46°F). If not used immediately, store diluted solution in refrigerator for up to 6 h. Do not freeze. Protect from light.

Drug Interactions

Antimicrobial effects may be reduced.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hot flashes, hypertension, palpitation, syncope, tachycardia (at least 5%).

CNS

Fatigue (43%); headache (22%); neuropathy (13%); malaise (9%); dizziness (8%); depression (7%); insomnia (6%); amnesia, anxiety, ataxia, confusion, convulsions, emotional lability, abnormal gait, hallucination, hyperkinesias, hypertonia, meningitis, somnolence, abnormal thinking, tremor (at least 5%).

Dermatologic

Alopecia (8%); pruritus (7%); folliculitis, seborrhea, dry skin (at least 5%).

EENT

Rhinitis (12%); abnormal vision (3%); conjunctivitis, deafness, earache, eye pain, taste perversion, tinnitus (at least 5%).

GI

Nausea (51%); diarrhea (34%); anorexia (21%); vomiting, abdominal pain (20%); stomatitis (9%); constipation (7%); tenesmus (4%); increased appetite, dysphagia, GI hemorrhage, gastritis, gingival bleeding, hemorrhoids, hepatomegaly, melena, dry mouth, tooth caries (at least 5%).

Genitourinary

Dysuria, nocturia, polyuria (at least 5%).

Hematologic-Lymphatic

Neutropenia (less than 1,000 cells/mm ³ [36%]); neutropenia (less than 500 cells/mm ³ [15%]); lymphadenopathy, splenomegaly (at least 5%).

Local

Injection site inflammation (at least 5%).

Metabolic-Nutritional

Dehydration, thirst (at least 5%).

Musculoskeletal

Rigors (19%); back pain (16%); arthralgia, myalgia (7%).

Respiratory

Cough (26%); dyspnea (23%); sinusitis (8%); hemoptysis, hiccups, pulmonary infiltration, increased sputum (at least 5%).

Miscellaneous

Fever (42%); opportunistic infection (40%); allergic reactions (21%); triad of back pain, flushing, and chest tightness (14%); increased sweating (12%); edema, chest pain (9%); flu-like symptoms (5%).

Precautions

Pregnancy

Category D .

Lactation

HIV-infected mothers should not breast-feed infants.

Children

Safety and efficacy not established.

Renal Function

Assess renal function before initiating therapy; adjust dose as necessary. Reduce dosage for renal function impairment.

Cardiac function

Ensure cardiac function is evaluated and documented by a history and physical examination before starting therapy and before each course of therapy. Ensure that LVEF is determined at a total cumulative dose of 320 mg/m ² and every 160 mg/m ² thereafter in patient with no prior therapy with anthracyclines, no evidence of cardiac disease, and no prior radiotherapy encompassing the heart. Ensure that LVEF is determined before starting therapy and at every total cumulative dose of 160 mg/m ² in patient with prior therapy with anthracyclines (doxorubicin dose greater than 300 mg/m ² or equivalent), preexisting cardiac disease, or prior radiotherapy encompassing the heart.

Daunorubicin dose

The dose of daunorubicin citrate liposomal is different from the dose of daunorubicin hydrochloride.

Extravasation risk

Local irritation or phlebitis may occur. Refer to your institution-specific protocol.

Overdosage

Symptoms

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

Patient Information

• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver that medication may cause a red coloration of the urine. Advise that this is not a problem and is expected because the medication is being eliminated in the urine.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; chest pain; fever, chills, or other signs of infection; unusual bleeding or bruising; pain, redness, or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting or appetite loss; persistent or worsening general body weakness.
• Advise patient, family, or caregiver that hair loss is a common side effect of therapy, but that this is usually reversible after therapy has been completed.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.