daunorubicin hydrochloride

daunorubicin hydrochloride Warning - Hazardous drug!

Cerubidine

Pharmacologic class: Anthracycline glycoside

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Administer into rapidly flowing I.V. infusion; never give I.M. or subcutaneously. Severe local tissue necrosis results if extravasation occurs.
• Myocardial toxicity (manifested most severely as potentially fatal congestive heart failure) may occur during therapy or months to years afterward. Incidence increases with total cumulative dose exceeding 550 mg/m² in adults, 300 mg/m² in children older than age 2, or 10 mg/kg in children younger than age 2.
• Therapeutic doses cause severe myelosuppression. Drug should be given only by physician experienced in leukemia chemotherapy, in facility with adequate diagnostic and treatment resources for monitoring drug tolerance and treating toxicity. Physician and facility must be capable of responding rapidly and completely to severe hemorrhagic conditions and overwhelming infection.
• Reduce dosage in patients with hepatic or renal impairment.

Action

Antimitotic and cytotoxic. Forms complexes with DNA by intercalation between base pairs. Inhibits topoisomerase II activity by stabilizing topoisomerase II complex; causes breaks in single- and double-stranded DNA. May also inhibit polymerase activity, influence regulation of gene expression, and cause free radical damage to DNA.

Availability

Injection: 5 mg/ml

Lyophilized powder for injection: 21.4 mg, 53.5 mg

⊘Indications and dosages

➣ Acute nonlymphocytic leukemia

Adults older than age 60: 30 mg/m²/day I.V. on days 1, 2, and 3 of first course and on days 1 and 2 of subsequent courses; given with cytarabine I.V. infusion (7 days for first course, 5 days for subsequent courses)

Adults younger than age 60: 45 mg/m²/day I.V. on days 1, 2, and 3 of first course and on days 1 and 2 of subsequent courses; given with cytarabine I.V. infusion (7 days for first course, 5 days for subsequent courses)

➣ Acute lymphocytic leukemia

Adults: 45 mg/m²/day I.V. on days 1, 2, and 3; vincristine I.V. on days 1, 8, and 15; prednisone P.O. on days 1 through 22, then tapered between days 22 and 29; then asparaginase I.V. on days 22 to 32

Children ages 2 and older: 25 mg/m²/day I.V. on first day every week; may be given in combination with vincristine I.V. on first day every week and prednisone P.O. daily

Dosage adjustment

• Renal or hepatic impairment

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:
• renal or hepatic impairment, bone marrow depression, cardiac disease, gout, infections
• elderly patients
• pregnant or breastfeeding patients.

Administration

• Follow facility policy for preparing and handling antineoplastics.
• If prescribed, premedicate with allopurinol to help prevent hyperuricemia.
☞ Give by I.V. route only.
• Reconstitute vial contents with 4 ml of sterile water for injection to yield 5 mg/ml solution.
• Don't mix with other drugs or heparin.
• Withdraw desired dosage into syringe containing 10 to 15 ml of normal saline solution; then inject into tubing or sidearm of compatible, rapidly flowing I.V. solution over 3 to 5 minutes. For intermittent infusion, mix with 100 ml of normal saline solution and infuse over 30 to 45 minutes.
☞ Take care to prevent extravasation, because drug causes severe local tissue necrosis. If extravasation occurs, stop infusion immediately; according to facility policy, intervene to avoid severe tissue necrolysis, severe cellulitis, thrombophlebitis, and painful induration.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

Adverse reactions

CV: cardiotoxicity

GI: acute nausea, vomiting, GI mucosal inflammation

GU: urine discoloration

Hematologic: bone marrow depression

Metabolic: hyperuricemia

Skin: rash, contact dermatitis, urticaria, reversible alopecia

Interactions

Drug-drug. Other antineoplastic, hepatotoxic, or myelosuppressive drugs: increased risk of toxicity

Drug diagnostic tests. Granulocytes: decreased count

Uric acid: increased level

Patient monitoring

☞ Observe I.V. site closely for extravasation.
• Monitor cardiac, renal, and hepatic function before each course of treatment.
• Evaluate CBC with white cell differential before each dose. Withhold dose if granulocyte count is below 750 cells/mm³.
• Monitor serum uric acid level.

Patient teaching

☞ Instruct patient to immediately report swelling, pain, burning, or redness at infusion site, as well as persistent nausea, vomiting, diarrhea, bloody stools, abdominal or chest pain, swollen arm or leg, difficulty breathing, palpitations, rapid heartbeat, or yellowing of skin or eyes.
• Inform patient that drug makes him more susceptible to infection. Caution him to avoid crowds and exposure to illness.
• Advise patient to minimize GI upset by eating small, frequent servings of healthy food, drinking plenty of fluids, and chewing gum.
• Tell patient that drug may redden his urine.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.