Daunorubicin; Uses, Dosage, Side Effects, Interactions

Daunorubicin; Uses, Dosage, Side Effects, Interactions

Daunorubicin is a very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in the treatment of LEUKEMIA and other NEOPLASMS. Daunorubicin is an Anthracycline Topoisomerase Inhibitor. The mechanism of action of daunorubicin is as a Topoisomerase Inhibitor. The chemical classification of daunorubicin is Anthracyclines.
Daunorubicin is an anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin. Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis.

Mechanism of Action of Daunorubicin

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.
Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms of anthracycline action involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a major critical factor that determines anthracycline resistance. Natural product, daunorubicin a toxic analogue of anthracycline is reduced to less toxic daunorubicinol by the AKR1B10, enzyme, which is overexpressed in most cases of smoking associate squamous cell carcinoma (SCC) and adenocarcinoma. In addition, AKR1B10 was discovered as an enzyme overexpressed in human liver, cervical and endometrial cancer cases in samples from uterine cancer patients. Also, the expression of AKR1B10 was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma in cervical cancer and estimated to have the potential as a tumor intervention target colorectal cancer cells (HCT-8) and diagnostic marker for non-small-cell lung cancer. This article presents the mechanism of daunorubicin action and a method to improve the effectiveness of daunorubicin by modulating the activity of AKR1B10.

Indications of Daunorubicin

  • For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.
  • Treatment of acute myeloid leukemia.
  • Acute Nonlymphocytic Leukemia
  • Acute Lymphocytic Leukemia
  • Acute erythroid leukemia
  • Acute monocytic leukemia
  • Leukemia Acute Myeloid Leukemia.
You Might Also Like   Fluocinolone Acetonide Scalp Oil - Uses, Indications

Contra-Indications of Daunorubicin

  • Severe infection
  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
  • Decreased function of bone marrow
  • Anemia
  • Decreased Blood Platelets
  • Decreased Neutrophils a Type of White Blood Cell
  • heart attack within the last 30 days
  • Disease of the Muscle of the Heart with Enlargement
  • Atrioventricular Heart Block
  • Bundle Branch Block
  • Abnormal heart rhythm
  • Heart Failure
  • Inflammation of the Middle Tissue Heart Muscle
  • liver problems
  • High Amount of Bilirubin in the Blood
  • Tingling
  • Pain
  • Redness and Edema of Hands and Feet
  • Pregnancy
  • A mother who is producing milk and breastfeeding
  • Dysfunction of Left Ventricle of Heart Without Symptoms
  • Anemia from Pyruvate Kinase and G6PD Deficiencies
  • Allergies to Anthracyclines

Dosage of Daunorubicin

Strengths: 20 mg; 5 mg/mL; 50 mg

Acute Nonlymphocytic Leukemia

  • Under 60 years of age: 45 mg/m2 IV over 2 to 5 minutes once a day on days 1, 2, and 3 for the first course and on days 1 and 2 for subsequent courses) with cytosine arabinoside (ara-C) intravenously once a day (usually for 7 days for the first course and 5 days for subsequent courses) as remission induction therapy.

Acute Lymphocytic Leukemia

For Remission Induction:

  • 45 mg/m2/day IV on days 1, 2, and 3 (along with vincristine, prednisone, and L-asparginase therapy)

Acute Nonlymphocytic Leukemia

  • Greater than or equal to 60 years of age: 30 mg/m2 IV over 2-5 minutes once a day on days 1, 2, and 3 for the first course and on days 1 and 2 for subsequent courses) with cytosine arabinoside (ara-C) intravenously once a day (usually for 7 days for the first course and 5 days for subsequent courses) as remission induction therapy.

Pediatric Dose for Acute Myeloid Leukemia

As a part of combination therapy: Induction

  • 30 to 60 mg/m2/day by continuous IV infusion on days 1 to 3 of cycle
    or
  • 20 mg/m2/day for 4 days every 14 days
You Might Also Like   Esmolol; Indications/Uses, Dosage, Side effects, Drug Interaction ,Pregnancy

Side Effects of Daunorubicin

Most Common

  • Pain, redness, swelling at the place of injection
  • Painful swallowing
  • Signs of anemia (e.g., feeling weak, dizzy, or short of breath)
  • Signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, cuts that don’t stop bleeding)
  • Signs of a blood clot in blood vessels, such as sudden vision change or dizziness, chest pain, pain and swelling in one leg muscle
  • Signs of an infection (e.g., fever over 38°C, chills or sweating, sore throat, coughing, redness or swelling around a cut, wound or catheter site, painful or difficult urination, unusual vaginal itching or discharge)

More Common

  • Hair loss, thinning of hair
  • Nausea and vomiting
  • Sores in the mouth and on the lips
  • Darkening of the soles, palms, or nails
  • Diarrhea
  • Fast or irregular heartbeat
  • Shortness of breath
  • Swelling of the feet and lower legs

Less Common

  • Cough or hoarseness accompanied by fever or chills
  • Darkening or redness of the skin (if you recently had radiation treatment)
  • Fast or irregular heartbeat
  • Fever or chills
  • Joint pain
  • Lower back or side pain accompanied by fever or chills
  • Pain at the injection site
  • Painful or difficult urination accompanied by fever or chills
  • Red streaks along the injected vein

Drug Interactions of Daunorubicin

Daunorubicin may interact with following drugs, supplements & may change the efficacy of drugs

  • antipsychotics (e.g., chlorpromazine, clozapine)
  • atorvastatin
  • “azole” antifungals (e.g., fluconazole, itraconazole, voriconazole)
  • bevacizumab
  • bupropion
  • calcium channel blockers (e.g., diltiazem, verapamil)
  • carbamazepine
  • carvedilol
  • celecoxib
  • ciprofloxacin
  • cyclosporine
  • dasatinib
  • desipramine
  • dexamethasone
  • hydrocortisone
  • loperamide
  • macrolide antibiotics (e.g., clarithromycin, erythromycin)
  • mercaptopurine
  • metronidazole
  • non-drowsy” antihistamines (e.g., cetirizine, desloratadine, loratadine)
  • norfloxacin
  • other anthracyclinecancer medications (e.g., daunorubicin, idarubicin)
  • other cancer medications (e.g., cyclophosphamide, doxetaxel, irinotecan, paclitaxel)
  • oxcarbazepine
  • pentobarbital
  • phenobarbital
  • phenytoin
  • prazosin
  • primidone
  • progesterone
  • propranolol
  • protease inhibitors (e.g., lopinavir, ritonavir, stavudine)
  • selegiline
  • SSRI antidepressants (e.g., fluoxetine, paroxetine, sertraline)
  • St. John’s wort
  • tacrolimus
  • tamoxifen
  • tetracycline
You Might Also Like   Vitamin B5 ; Symptoms, Food Source, Health Benefit

Pregnancy Category

FDA Pregnancy Category: D

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you are a breastfeeding mother and are taking doxorubicin, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. Children who receive doxorubicin are at an increased risk of developing leukemia. Children may also be more susceptible to the effects of this medication on the heart.

References

Daunorubicin

Loading

If the article is helpful, please Click to Star Icon and Rate This Post!
[Total: 0 Average: 0]

About the author

Translate »