Daunorubicin
Daunorubicin (Cerubidine)
Daunorubicin
(daw-noh- ROO-bih-sin)
Pregnancy Category: D Cerubidine (Abbreviation: DNR) (Rx)
Daunorubicin Citrate Liposomal
Daunorubicin Citrate Liposomal
Daunorubicin
(daw-noh- ROO-bih-sin)
Pregnancy Category: D DaunoXome (Rx)

Classification: Antineoplastic, antibiotic

See Also: See also Antineoplastic Agents .

Action/Kinetics: Anthracycline antibiotic produced by Streptomyces coeruleorubidus or S. peucetius. The liposomal product contains an aqueous solution of the citrate salt of daunorubicin encapsulated within lipid vesicles which are composed of a lipid bilayer of distearoylphosphatidylcholine and cholesterol. Most active in the S phase of cell division but is not cell-cycle specific. Inhibits synthesis of nucleic acid by inserting into the double helix of DNA. Also possesses immunosuppressive, cytotoxic, and antimitotic activity. Rapidly cleared from the plasma. The liposomal preparation helps protect daunorubicin from chemical and enzymatic breakdown; also, it minimizes protein binding and decreases uptake by normal tissues. Is released from the liposomal preparation over time and improves selectivity for solid tumors. Metabolized to the active daunorubinicol. t 1/2: daunorubicin (nonliposomal product), 18.5 hr; daunorubinicol, 27 hr. t 1/2, elimination: 4.4 hr for liposomal form. Drug rapidly taken up by heart, kidneys, lung, liver, and spleen. Chiefly excreted in bile (40%) and unchanged in urine (25%). Does not pass blood-brain barrier.

Uses: Acute nonlymphocytic leukemia in adults (myelogenous, erythroid, monocytic). When combined with cytarabine, effectiveness is increased. Acute lymphocytic leukemia in adults and children (increased effectiveness when combined with vincristine and prednisone). The lioposomal product is a first-line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma. Investigational: Ewing's sarcoma, chronic myelocytic leukemia, neuroblastoma, non-Hodgkin's lymphomas, Wilms' tumor.

Contraindications: Lactation. Hypersensitivity to previous doses.

Special Concerns: Use with caution in preexisting heart disease or bone marrow depression, renal or hepatic failure. Safety and effectiveness have not been determined in children or geriatric clients.

Side Effects: Myocardial toxicity: Potentially fatal CHF, especially if total dosage exceeds 550 mg/m ² for adults, 300 mg/m ² for children more than 2 years of age, and 10 mg/kg for children less than 2 years of age. Mucositis (3-7 days after administration), red-colored urine, hyperuricemia. Severe tissue necrosis if extravasation occurs. Cross-resistance with doxorubicin (produced by similar microorganism) and vinca alkaloids. Hyperuricemia may occur due to lysis of leukemic cells; give allopurinol as a precaution, before starting antileukemic therapy. For the liposomal product. CNS: Fatigue, headache, neuropathy, malaise, dizziness, depression, insomnia, amnesia, anxiety, ataxia, confusion, seizures, emotional lability, abnormal gait, hallucinations, hyperkinesia, hypertonia, meningitis, somnolence, abnormal thinking, tremors. Hematologic: Myelosuppression, especially of the granulocytic series. Neutropenia. CV: Cardiomyopathy associated with a decrease in left ventricular ejection fraction (especially in clients who have received prior anthracyclines or who have preexisting cardiac disease). Also, hot flushes, hypertension, palpitation, syncope, tachycardia. GI: Nausea, diarrhea, anorexia, abdominal pain, vomiting, stomatitis, constipation, increased appetite, dysphagia, GI hemorrhage gastritis, gingival bleeding, hemorrhoids, hepatomegaly, melena, dry mouth, tooth caries. Respiratory: Cough, dyspnea, rhinitis, sinusitis, hemoptysis, hiccoughs, pulmonary infiltration, increased sputum. Musculoskeletal: Rigors, back pain, myalgia, arthralgia. Dermatologic: Alopecia, pruritus, foliculitis, seborrhea, dry skin. GU: Dysuria, nocturia, polyuria. Ophthalmic: Abnormal vision, conjunctivitis, eye pain. Otic: Deafness, ear pain, tinnitus. Miscellaneous: Fever, allergic reactions, sweating, chest pain, edema, taste perversion, tenesmus, flu-like symptoms, opportunitistic infections, inflammation at injection site, lymphadenopathy, splenomegaly, dehydration, thirst. Back pain, flushing, and chest tightness have been reported within the first 5 min of the infusion.

Laboratory Test Alterations: Hyperuricemia secondary to rapid lysis of leukemic cells.

Overdose Management: Symptoms: Granulocytopenia, fatigue, N&V.; Also, extension of side effects.

How Supplied: Injection: 5 mg/mL; Powder for injection: 20 mg

Dosage
?IV Infusion of Daunorubicin Acute nonlymphocytic leukemia.
Adults: Daunorubicin, 45 mg/m ²/day on days 1, 2, and 3 of first course and days 1 and 2 of additional courses; cytosine arabinoside (Ara-c) 100 mg/m ²/day, by IV infusion, for 7 days during first course and for 5 days during any additional courses of treatment. Some recommend reducing the dose of daunorubicin to 30 mg/m ² in clients 60 years of age and older. Up to three courses may be required.
Acute lymphocytic leukemia.
Adults: Daunorubicin, 45 mg/m ², IV, on days 1, 2, and 3; vincristine, IV, on days 1, 8, and 15; prednisone, PO, 40 mg/m ²/day for days 1-22 and then taper between days 22 and 29; and, l-asparaginase, IV, 500 IU/kg/day on days 22-32.
Acute lymphocytic leukemia.
Children: Daunorubicin, 25 mg/m ², and vincristine, 1.5 mg/m ², each IV, on day 1 every week with prednisone, 40 mg/m ², PO, daily. Usually four courses will induce remission. NOTE: Calculate the dose on the basis of milligrams per kilogram if the child is less than 2 years of age or if the body surface is less than 0.5 m ².
Acute nonlymphocytic leukemia.
Geriatric clients: 30 mg/m ² on days 1, 2, and 3 of the first course and days 1 and 2 of the second course in combination with cytarabine.
?IV infusion of Daunorubicin Citrate Liposomal Advanced HIV-associated Kaposi's sarcoma.
40 mg/m ² given over 1 hr. Dose is repeated q 2 weeks. This regimen is continued until there is progression of the disease or other complications of HIV disease preclude continued therapy.
Reduce dosage for renal or hepatic disease. Recommended dose for liposomal product: three-fourths of normal dose if serum bilirubin is 1.2 to 3 mg/dL; one-half of normal dose if serum bilirubin is less than 3 mg/dL and serum creatinine is greater than 3 mg/dL.