Idarubicin is a semisynthetic 4-dimethoxy analog of the antineoplastic anthracycline antibiotic daunorubicin. Idarubicin intercalates into DNA and interferes with the activity of topoisomerase II, thereby inhibiting DNA replication, RNA transcription, and protein synthesis. Due to its high lipophilicity, idarubicin penetrates cell membranes more efficiently than other anthracycline antibiotic compounds.

Mechanism of Action of Idarubicin

Idarubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Idarubicin 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.

Indications of Idarubicin

  • For the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7.
  • Acute Myeloid Leukemia
  • Acute Nonlymphocytic Leukemia
  • Leukemia Acute Myeloid Leukemia.

Contra-Indications of Idarubicin

  • 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 Idarubicin

Strengths: 1 mg/mL; 5 mg; 10 mg; 20 mg

Acute Myeloid Leukemia

  • 12 mg/m2 daily for 3 days by slow (10 to 15 min) IV administration in combination with cytarabine
  • Maximum recommended cumulative lifetime dose for the IV formulation: 150 mg/m2
  • In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered.
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Acute Nonlymphocytic Leukemia

  • 12 mg/m2 daily for 3 days by slow (10 to 15 min) IV administration in combination with cytarabine
  • Maximum recommended cumulative lifetime dose for the IV formulation: 150 mg/m2
  • In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered.

Side Effects of Idarubicin

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 Idarubicin

Idarubicin 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
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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 effects of this medication on the heart.

References

Idarubicin