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Does Adriamycin cause heart failure?

Medically reviewed by Carmen Fookes, BPharm Last updated on Apr 21, 2020.

Official Answer

by Drugs.com
  • Yes. There is a risk of people developing cardiotoxicity including heart failure with Adriamycin use
  • The risk increases as the cumulative dose of Adriamycin increases
  • The probability of developing congestive heart failure ranges from 1.5% for a cumulative dose of 300 mg/m2 of Adriamycin up to 20.5-21% for a cumulative dose of 500-728 mg/m2 of Adriamycin 
  • The risk is higher if Adriamycin is used with other chemotherapy agents, such as cyclophosphamide, fluorouracil, or vincristine
  • Cardiotoxicity including heart failure is also more likely to occur in seniors, people exposed to Adriamycin at a young age, concomitant use of other cardiotoxic drugs, calcium channel blockers, pre-existing heart disease, or prior radiation therapy to the heart
  • People prescribed the monoclonal antibody trastuzumab have a much higher risk of cardiotoxicity including heart failure with Adriamycin at lower cumulative doses.

Cardiotoxicity is one of the most common potential long-term side effects of Adriamycin.

Cardiotoxicity means permanent damage to the muscles of the heart or the functioning of the heart. Cardiotoxicity can be severe with Adriamycin treatment and may develop late during therapy, or within two to three months after the treatment has ended.

Symptoms include signs or symptoms of heart failure, including a reduced ability of the left side of the heart to pump (called LVEF or left ventricular ejection fraction), a fast heartbeat, shortness of breath, fluid on the lungs, as well as other related symptoms.

The probability of developing cardiotoxicity increases the higher the cumulative dose of Adriamycin that has been given, for example, the probability is:

  • 1-2% for a total cumulative dose of 300 mg/m2 of Adriamycin
  • 3-5% for a total cumulative dose of 400 mg/m2 of Adriamycin
  • 5-8% for a total cumulative dose of 450 mg/m2 of Adriamycin
  • 6-20% for a total cumulative dose of 500 mg/m2 of Adriamycin.

The probability of developing congestive heart failure has been reported as:

  • 1.5% for a cumulative dose of 300 mg/m2 of Adriamycin
  • 3-4.9% for a cumulative dose of 400-430 mg/m2 of Adriamycin
  • 7-7.7% for a cumulative dose of 450-475 mg/m2 of Adriamycin
  • 20.5-21% for a cumulative dose of 500-728 mg/m2 of Adriamycin.

The risk of developing heart failure rapidly increases with increasing cumulative doses above 400 mg/m2 and when Adriamycin is used with other chemotherapy agents, such as cyclophosphamide, fluorouracil, or vincristine.

Cardiotoxicity may also occur at lower doses in seniors, people exposed to Adriamycin at a young age, concomitant use of other cardiotoxic drugs, calcium channel blockers, pre-existing heart disease, or prior radiation therapy to the heart.

People prescribed the monoclonal antibody trastuzumab have a much higher risk of cardiotoxicity with Adriamycin at lower cumulative doses.

The package insert for Adriamycin states that lifetime cumulative doses above 550 mg/m2 (21-day cycles) are associated with an increased risk of cardiomyopathy.

In people at higher risk of cardiotoxicity, the maximum cumulative dose of doxorubicin should be limited to less than 400 mg/m2.

In certain cases, people who have received total cumulative doses of 450 mg/m2 may be considered for further therapy up to a total cumulative dose of 700 mg/m2 provided they undergo cardiac assessment and are deemed to be suitable to continue treatment.

Dexrazoxane may be used for cardioprotection in patients with advanced or metastatic cancer who are at risk of developing cardiotoxicity when receiving Adriamycin.

References
  • Adriamycin (doxorubicin) for injection. FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/062921s022lbl.pdf
  • Doxorubicin (Rx) Medscape.com https://reference.medscape.com/drug/doxorubicin-342120
  • Rahman AM, Yusuf SW, Ewer MS. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine. 2007;2(4):567–583.
  • Doxorubicin. Drugs.com Oct 7 2019. https://www.drugs.com/dosage/doxorubicin.html

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