Daunorubicin Hydrochloride

Pronunciation: (DAW-no-RUE-bih-sin)
Class: Anthracycline

Trade Names

Cerubidine
- Lyophilized powder for injection 20 mg vial with 100 mg mannitol added
- Solution for injection 5 mg/mL, 4 mL vial

Pharmacology

Antimitotic and cytotoxic activity.

Pharmacokinetics

Distribution

Extensive and rapid protein binding. Highest concentrations in spleen, kidneys, liver, lungs, and heart.

Metabolism

Extensively metabolized in liver and other tissues to daunorubicinol (active).

Elimination

t _½ is 18.5 h (daunorubicin) and 26.7 h (daunorubicinol). Approximately 25% excreted in active form in the urine and 40% by biliary excretion.

Indications and Usage

Acute lymphocytic leukemia.

Unlabeled Uses

Chronic myelogenous leukemia, Kaposi sarcoma.

Contraindications

None well documented.

Dosage and Administration

Acute Nonlymphocytic Leukemia (Combination Therapy)
Adults (younger than 60 yr of age)

IV Daunorubicin 45 mg/m ² /day on days 1 to 3 of first course and days 1 to 2 of subsequent courses. May require up to 3 courses.

Adults (older than 60 yr of age)

IV Daunorubicin 30 mg/m ² /day on days 1 to 3 of first course and days 1 to 2 of subsequent courses. May require 3 courses.

Acute Lymphocytic Leukemia (Combination Therapy)
Adults

IV Daunorubicin 45 mg/m ² /day on days 1 to 3.

Acute Lymphocytic Leukemia
Children (2 yr of age and older)

IV Daunorubicin 25 mg/m ² on day 1 every wk with vincristine and oral prednisone. Generally, complete remission will be obtained with 4 courses of therapy. If after 4 courses the patient is in partial remission, an additional 1 or, if necessary, 2 courses may be given.

Children (younger than 2 yr of age or under 0.5 m ² BSA)

IV Calculate dosage on the basis of weight (mg/kg) instead of BSA.

Dosage Adjustment for Renal or Hepatic Function Impairment

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

Lifetime Cumulative Doses Above Which Frequency of Cardiotoxicity Increases
Adults

IV No more than 550 mg/m ² .

Adults having received mediastinal radiation

IV No more than 400 mg/m ² .

Children (2 yr of age and older)

IV No more than 300 mg/m ² .

Children (younger than 2 yr of age)

IV No more than 10 mg/m ² .

General Advice

Reconstitute vials of powder with sterile water for injection for a final concentration of 5 mg/mL. Shake vial gently to dissolve contents. Maximum concentration of daunorubicin for administration is 5 mg/mL; more concentrated solutions are hyperosmolar.
Withdraw the desired dose into a syringe containing 10 to 15 mL of normal saline; inject into a rapidly flowing IV infusion of 5% glucose or normal saline solution.
Although reconstituted solution is chemically stable under refrigeration longer, it contains no preservative; use within 24 h. Protect from sunlight.
Color change of solution from red to blue-purple indicates decomposition.
Reconstituted solution can be diluted in 100 mL of dextrose 5% or sodium chloride 0.9% and infused IV over 30 to 45 min. However, many health care providers consider the risk of extravasation unacceptable unless infused through a central venous catheter.
Do not mix with other drugs or heparin.

Storage/Stability

Store powder at room temperature (59° to 86°F). Protect from light. Refrigerate unopened vials of solution. Protect from light.

Drug Interactions

Cyclophosphamide

May result in increased daunorubicin toxicity.

Hepatotoxic medications

May impair liver function and increase the risk of toxicity.

Myelosuppressive agents

Dosage reduction of daunorubicin may be required.

Quinolone antibiotics

Daunorubicin may decrease the oral absorption of quinolone antibiotics.

Laboratory Test Interactions

Hyperuricemia

May be induced secondary to a rapid lysis of leukemic cells. As a precaution, administer allopurinol prior to initiating antileukemic therapy.

Adverse Reactions

Cardiovascular

Delayed dose-related cardiomyopathy; acute arrhythmias.

Dermatologic

Alopecia; rash; contact dermatitis; urticaria; radiation recall; nail hyperpigmentation.

GI

Nausea; vomiting; mucositis; esophagitis; diarrhea; abdominal pain.

Hematologic

Bone marrow suppression.

Hypersensitivity

Anaphylaxis.

Miscellaneous

Fever; chills.

Precautions

Monitor

Attaining a normal appearing bone marrow may require no more than 3 courses of induction therapy. Evaluate bone marrow following recovery from the previous induction course to determine the need for a further course of induction treatment. Monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.

Pregnancy

Category D .

Lactation

Advise mothers to discontinue nursing.

Children

Cardiotoxicity may be more frequent and occur at lower cumulative doses.

Elderly

Cardiotoxicity may be more frequent. Use caution in patients who have inadequate bone marrow reserves because of old age.

Renal Function

Some health care providers recommend not giving daunorubicin to patients with a bilirubin above 5 mg/dL. Reduce dose.

Hepatic Function

Some health care providers recommend not giving daunorubicin to patients with a bilirubin above 5 mg/dL. Reduce dose.

ECG

Monitor ECG and systolic ejection fraction as the maximum cumulative lifetime dose approaches. Certain ECG changes and a decrease in the systolic injection fraction from pretreatment baseline may aid in recognizing those patients at greatest risk. A decrease of at least 30% in limb lead QRS voltage has been associated with significant risk of drug-induced cardiomyopathy. Perform an ECG or determine systolic ejection fraction before each course.

Extravasation risk

Local irritation of phlebitis may occur. Refer to the institution's specific protocol.

Health care provider administration

It is recommended that daunorubicin be administered only by health care providers who are experienced in leukemia chemotherapy.

Myelosuppression

Occurs when used in therapeutic doses; this may lead to infection or hemorrhage.

Myocardial toxicity

Potentially fatal CHF may occur when total cumulative dosage exceeds 400 to 550 mg/m ² in adults, 300 mg/m ² in children older than 2 yr of age, or 10 mg/kg in children younger than 2 yr of age. This may occur during therapy or several months to years after therapy.

Previous cumulative dose

Do not use in patients who have previously received the recommended maximum cumulative dose of either doxorubicin or daunorubicin.

Secondary leukemias

There have been reports of secondary leukemias in patients exposed to daunorubicin when used in combination with other antineoplastic agents or radiation therapy.

Patient Information

Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve maximum benefit possible.
Review dosing schedule with patient, family, or caregiver.
Advise patient, family, or caregiver that medication will usually 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 that medication may cause hair loss but that this is reversible when therapy is stopped.
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; sores in mouth; 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.
Caution women of childbearing potential to avoid becoming pregnant while being treated.
Advise patient that following discharge from the hospital that frequent follow-up visits, ECGs, or heart function tests, and laboratory tests will be required to monitor therapy and to keep appointments.