Drug information of Daunorubicin

Daunorubicin

Drug group:

A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms.

Mechanism of effect

Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Pharmacodynamic

Daunorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics.

However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Daunorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

Pharmacokinetics

  • Protein Bound: 50-60%
  • Half-life: 14-20 hr (parent drug), 24-48 hr (daunorubicinol)
  • Vd: 20-39.2 L/kg
  • Metabolism: Hepatic
  • Metabolites: Daunorubicinol
  • Clearance: 17.3 mL/min
  • Excretion: Feces (40%) & urine (25%)

Drug indications

Acute Myeloid Leukemia

Dosage

Adult

Acute Nonlymphocytic Leukemia

In combination with cytarabine 100 mg/m²/day IV for 7 days first course, for 5 days subsequent courses 

<60 years old: 45 mg/m² IVP days 1, 2, 3 first course; days 1, 2 subsequent courses

>60 years old: 30 mg/m² IVP days 1, 2, 3 first course; days 1, 2 subsequent courses

Monitor: Cardiac, renal, hepatic function

Acute Lymphocytic Leukemia

45 mg/m² IVP days 1, 2, 3 

Monitor: Cardiac, renal, hepatic function

Pediatric

Acute Nonlymphocytic Leukemia and Acute Lymphocytic Leukemia

<2 years old or <0.5 m² BSA: 1 mg/kg IVP qWeek 

>2 years old or >0.5 m² BSA: 25 mg/m² IVP qWeek

Monitor: Cardiac, renal, hepatic function

Drug contraindications

allergic reaction

Side effects

Diarrhea , nausea , vomiting

Alerts

  • Risk of severe cardiotoxicity (including CHF) & myelosuppression
  • Caution in hepatic/renal impairment
  • Children may be more sensitive to cardiotoxic effects than adults
  • Avoid pregnancy
  • Secondary leukemias reported when used in combination with radiation or chemotherapy
  • Black Box Warnings
  • The drug should be administered under the supervision of an experienced leukemia-chemotherapy physician. Physician must be capable of responding rapidly to severe hemorrhagic conditions or overwhelming infection.
  • Administer daunorubicin into a rapidly flowing IV infusion. Severe local tissue necrosis will result if extravasation occurs. Do not administer IM or SC.
  • Cumulative dosage that exceeds 400 to 550 mg/m² in adults, 300 mg/m² >2 years of age, or 10 mg/kg in children <2 years of age may result in a severe and potentially fatal myocardial toxicity including congestive heart failure; this may occur during therapy or several months to years after therapy.
  • Severe myelosuppression that could lead to infection or hemorrahage may occur when used at therapeutic doses
  • Dosage adjustment recommended in patients with renal or hepatic impairment

Points of recommendation

  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
  • To help with mouth sores, use a soft toothbrush or cotton swabs and rinse the mouth. Do not use mouth rinses that have alcohol in them.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • You will need to have heart function tests while taking daunorubicin. Talk with the doctor.
  • Other drugs will be given with daunorubicin   to help avoid side effects.
  • Talk with your doctor before getting any vaccines. Use with daunorubicin   may either raise the chance of an infection or make the vaccine not work as well.
  • This medicine may cause you to not be able to get pregnant. Talk with the doctor.
  • Use birth control that you can trust to prevent pregnancy while taking daunorubicin.
  • If you are pregnant or you get pregnant while taking daunorubicin, call your doctor right away.

Pregnancy level

D


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