Cerubidine

Cerubidine

 [sĕ-roo´bĭ-dēn]
trademark for a preparation of daunorubicin, an antitumor antibiotic.

daunorubicin hydrochloride

FDA Box 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.

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.

DAUNOrubicin hydrochloride

(daw-noe-roo-bi-sin hye-dro-klor-ide) ,

Cerubidine

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: anthracyclines
Pregnancy Category: D

Indications

In combination with other antineoplastics in the treatment of leukemias.

Action

Forms a complex with DNA, which subsequently inhibits DNA and RNA synthesis (cell-cycle phase-nonspecific).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones. Also has immunosuppressive properties.

Pharmacokinetics

Absorption: Administered IV only, resulting in complete bioavailability.
Distribution: Widely distributed. Crosses the placenta.
Metabolism and Excretion: Extensively metabolized by the liver. Converted partially to a compound that also has antineoplastic activity (daunorubicinol); 40% eliminated by biliary excretion.
Half-life: Daunorubicin —18.5 hr. Daunorubicinol—26.7 hr.

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
IV 7–10 days10–14 days21 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity to daunorubucin or any other components in the formulation;Symptomatic HF/arrhythmias;Pregnant or lactating women.
Use Cautiously in: Active infections or decreased bone marrow reserve;Geriatric patients or patients with other chronic debilitating illnesses (dosage reduction recommended for patients ≥60 yr);May reactivate skin lesions produced by previous radiation therapy;Hepatic or renal impairment (dosage reduction recommended if serum creatinine >3 mg/dL or serum bilirubin >1.2 mg/dL);Patients who have received previous anthracycline therapy or who have underlying cardiovascular disease (increased risk of cardiotoxicity);Patients with child-bearing potential.

Adverse Reactions/Side Effects

Ear, Eye, Nose, Throat

  • rhinitis (most frequent)
  • abnormal vision
  • sinusitis

Cardiovascular

  • cardiotoxicity (life-threatening)
  • arrhythmias

Gastrointestinal

  • nausea (most frequent)
  • vomiting (most frequent)
  • esophagitis
  • hepatoxicity
  • stomatitis

Genitourinary

  • red urine (most frequent)
  • gonadal suppression

Dermatologic

  • alopecia (most frequent)

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • phlebitis at IV site (most frequent)

Metabolic

  • hyperuricemia

Miscellaneous

  • chills
  • fever

Interactions

Drug-Drug interaction

Additive myelosuppression with other antineoplastics.May decrease antibody response to live-virus vaccines and increase risk of adverse reactions.Cyclophosphamide increases the risk of cardiotoxicity.Increased risk of hepatic toxicity with other hepatotoxic agents.

Route/Dosage

Other dose regimens are used. In adults, cumulative dose should not exceed 550 mg/m2 (450 mg/m2 if previous chest radiation)
Intravenous (Adults <60 yr) 45 mg/m2/day for 3 days in first course, then for 2 days of second course (as part of combination regimen).
Intravenous (Adults ≥60 yr) 30 mg/m2/day for 3 days in first course, then for 2 days of second course (as part of combination regimen).
Intravenous (Children >2 yr) 25 mg/m2 once weekly (as part of combination regimen). In children <2 yr or BSA <0.5 m2, dosage should be determined on a mg/kg basis.

Availability (generic available)

Powder for injection: 20 mg/vial
Solution for injection: 5 mg/mL in 4-mL vials (20 mg)

Nursing implications

Nursing assessment

  • Monitor vital signs before and frequently during therapy.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Assess IV site frequently for inflammation or infiltration. Instruct patient to notify nurse immediately if pain or irritation at injection site occurs. If extravasation occurs, infusion must be stopped and restarted in another vein to avoid damage to subcut tissue. Notify physician immediately. Daunorubicin is a vesicant. Standard treatments include local injections of steroids and application of ice compresses.
  • Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting, which, although mild, may persist for 24–48 hr. Administration of an antiemetic before and periodically during therapy and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status. Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of the urine may be used to help prevent urate stone formation.
  • Assess patient for evidence of cardiotoxicity, which manifests as HF (peripheral edema, dyspnea, rales/crackles, weight gain, jugular venous distention) and usually occurs 1–6 mo after initiation of therapy. Chest x ray, echocardiography, ECGs, and radionuclide angiography determination of ejection fraction may be ordered before and periodically throughout therapy. A 30% decrease in QRS voltage and decrease in systolic ejection fraction are early signs of cardiotoxicity. Patients who receive total cumulative doses >550/mm2, who have a history of cardiac disease, or who have received mediastinal radiation are at greater risk of developing cardiotoxicity. May be irreversible and fatal, but usually responds to early treatment.
  • Lab Test Considerations: Monitor uric acid levels.
    • Daunorubicin hydrochloride: Monitor CBC and differential before and periodically throughout therapy. The leukocyte count nadir occurs 10–14 days after administration. Recovery usually occurs within 21 days after administration of daunorubicin.
    • Monitor AST, ALT, LDH, and serum bilirubin. May cause transiently ↑ serum alkaline phosphatase, bilirubin, and AST concentrations.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Decreased cardiac output (Side Effects)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings. Do not confuse daunorubicin hydrochloride (Cerubidine) with daunorubicin citrate liposome (DaunoXome) or with doxorubicin (Adriamycin, Rubex)or doxorubicin hydrochloride liposome (Doxil). To prevent confusion, orders should include generic and brand name.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
  • Intravenous: Reconstitute each 20 mg with 4 mL of sterile water for injection for a concentration of 5 mg/mL. Shake gently to dissolve. Reconstituted medication is stable for 24 hr at room temperature, 48 hr if refrigerated. Protect from sunlight.
    • Do not use aluminum needles when reconstituting or injecting daunorubicin, as aluminum darkens the solution.
  • Intravenous Administration
  • pH: 4.5–6.5.
  • Diluent: Dilute further in 10–15 mL of 0.9% NaCl. Administer direct IV push through Y-site into free-flowing infusion of 0.9% NaCl or D5W.
  • Rate: Administer over at least 2–3 min. Rapid administration rate may cause facial flushing or erythema along the vein.
  • Intermittent Infusion: Diluent: May also be diluted in 50–100 mL of 0.9% NaCl.
  • Rate: Administer 50 mL over 10–15 min or 100 mL over 30–45 min.
  • Y-Site Compatibility: amifostine, etoposide, filgrastim, gemcitabine, granisetron, melphalan, methotrexate, ondansetron, sodium bicarbonate, teniposide, thiotepa, vinorelbine
  • Y-Site Incompatibility: allopurinol, aztreonam, cefepime, fludarabine, lansoprazole, piperacillin/tazobactam
  • Additive Incompatibility: Manufacturer does not recommend admixing daunorubicin hydrochloride.

Patient/Family Teaching

  • Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patient should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
  • Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis pain may require management with opioid analgesics. Period of highest risk is 3–7 days after administration of dose.
  • Instruct patient to notify health care professional immediately if irregular heartbeat, shortness of breath, or swelling of lower extremities occurs.
  • Discuss with patient possibility of hair loss. Explore methods of coping. Regrowth of hair usually begins within 5 wk after discontinuing therapy.
  • Inform patient that medication may turn urine reddish color for 1–2 days after administration.
  • Inform patient that this medication may cause irreversible gonadal suppression. Advise patient that this medication may have teratogenic effects. Contraception should be used during therapy and for at least 4 mo after therapy is concluded.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Improvement of hematologic status in patients with leukemia.

Cerubidine

a trademark for an antineoplastic (DAUNOrubicin hydrochloride).
References in periodicals archive ?
For example, the chemotherapy drug daunorubicin is FDA approved "for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults," Cerubidine (Daunorubicin Hydrochloride) Injection, Powder, for Solution [Bedford Laboratories], DAILYMED, http://dailymed.
NASDAQ:CHIR) announced Monday that its joint-venture business with Ben Venue Laboratories of Bedford, Ohio, has purchased exclusive rights to Cerubidine (daunorubicin hydrochloride) for injection, a chemotherapeutic product for treatment of certain leukemias, from Wyeth-Ayerst Laboratories, a division of American Home Products Corp.
Under terms of the agreement, Wyeth-Ayerst will assign all of its trademark and technology rights with respect to Cerubidine to the venture, and will provide the venture with its customer lists.
As one of the mainstay therapies for leukemia, Cerubidine represents a significant addition to Chiron's expanding line of oncology products that includes Proleukin and Aredia," said Edward Kenney, vice president marketing and sales of Chiron Therapeutics.