Epirubicin; Uses, Dosage, Side Effects, Interactions

Epirubicin is an anthracycline which is the 4′-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Epirubicin is an Anthracycline Topoisomerase Inhibitor. The mechanism of action of epirubicin is as a Topoisomerase Inhibitor. The chemical classification of epirubicin is Anthracyclines.
Epirubicin is a 4′-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin. Epirubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation.

Mechanism of Action of Epirubicin

Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin 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. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
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Epirubicin is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical and biological functions within eukaryotic cells, the precise mechanisms of epirubicin’s cytotoxic and/or antiproliferative properties have not been completely elucidated. Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis. Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to result from these or other possible mechanisms.

Indications of Epirubicin

  • For use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.
  • Ellence Injection is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer. /Included in US product labeling/
  • Antibiotics, Antineoplastic; Topoisomerase II Inhibitors
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Contra-Indications of Epirubicin

  • Severe infection
  • Severely Decreased Activity of the Bone Marrow
  • Anemia
  • Decreased Blood Platelets
  • Decreased Neutrophils a Type of White Blood Cell
  • Heart attack
  • Heart attack within the last 30 days
  • Disease of the Muscle of the Heart with Enlargement
  • Abnormal heart rhythm
  • Life-Threatening Irregular Heart Rhythm
  • Chronic heart failure
  • Suddenly serious symptoms of heart failure
  • Painful
  • Red or Swollen Mouth
  • Severe liver disease
  • Severe renal impairment
  • High Amount of Bilirubin in the Blood
  • Pregnancy
  • A mother who is producing milk and breastfeeding
  • Allergies to Anthracyclines

Dosage of Epirubicin

Strengths: 2 mg/mL; 50 mg; 200 mg

Breast Cancer – Adjuvant

For use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer

  • Starting Dose: 100 to 120 mg/m2 by intravenous infusion every 3 to 4 weeks. The total dose may either be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle.

Side Effects of Epirubicin

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)
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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 Epirubicin

Epirubicin 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
  • azathioprine
  • bevacizumab
  • cimetidine
  • cyclophosphamide
  • daunorubicin
  • doxorubicin
  • mercaptopurine
  • 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
  • progesterone
  • propranolol
  • protease inhibitors (e.g., lopinavir, ritonavir, stavudine)
  • selegiline
  • SSRI antidepressants (e.g., fluoxetine, paroxetine, sertraline)
  • St. John’s wort
  • tacrolimus
  • tamoxifen
  • tetracycline

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.

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References

Epirubicin