Doxorubicin is an anthracycline class medication used in the management and treatment of various types of malignancies and tumors.
Non-FDA approved indications include:
Doxorubicin is one of the cytotoxic, anthracycline agents derived from Streptomyces spp. The anthracycline class of agents has similar mechanisms of action and work by intercalating between the DNA base pairs causing uncoiling of the DNA helical structure. This action causes inhibition of DNA synthesis and affects the activity of DNA topoisomerase II. Anthracyclines can also form free radicals which can target and damage rapidly growing cells.
Doxorubicin is a major substrate of cytochrome P450, CYP3A4, CYP2D6, and P-glycoprotein (Pgp). There have been several clinically significant interactions reported with other inhibitors of CYP3A4, CYP2D6, and/or Pgp that can increase doxorubicin concentration resulting in more or worsening side effects and toxicity at lower dosages.
Doxorubicin is available as a powder for injection or as a liquid solution [2 mg/mL] administered intravenously (IV) via a central line as a continuous infusion.
Adult dosing: 60 to 75 mg/m2 intravenously (IV) every 21 days OR
Due to the side effect profile and toxicity of doxorubicin, patients are only allowed a lifetime dose of 550 mg/m2. They are required to have close follow-up and monitoring of blood counts, liver function, and heart function studies.
Due to the cardiotoxic profile of doxorubicin, baseline left ventricular ejection fraction (LVEF) should be assessed and monitored routinely using an echocardiogram. An LVEF drop of greater than 10% from baseline is considered indicative cardiotoxicity, and immediate intervention by physicians and the healthcare team is required. An alternative to echocardiogram monitoring is radionuclide ventriculography, such as multigated acquisition angiogram (MUGA) or equilibrium radionuclide angiogram (ERNA) scans, although less frequently used.
Obtain baseline complete blood counts (CBC), hepatic enzymes, and tests of hepatic function.
Doxorubicin has been a mainstay in treating various cancers for many years, and members of the health care team must be aware and up to date on the indications, interaction, adverse effects, and other pharmacodynamic and pharmacokinetic factors that can affect successful therapy implementation, and lead to improved patient outcomes.
Prescribing and monitoring doxorubicin requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, and physicians in different specialties, including a primary medical doctor (internal medicine), cardiologist, and hematologist/oncologist.
Proper monitoring for complications, in particular, cardiac and hepatic, is indicated as a retrospective study reported cardiotoxicity in 26%, and the 1-year mortality with doxorubicin-induced cardiotoxicity is as high as 50%. Research has also shown cardiotoxicity to be the leading cause of death in patients taking anthracyclines, as seen by several extensive randomized clinical retrospective studies. [Level 1]
Regularly monitor complete blood counts and metabolic panels to monitor for myelosuppression. The medical team should respond and assess significant changes to consider halting the drug when indicated. This monitoring function often falls to the clinical pharmacist, who will track the necessary lab work and inform the ordering clinician regarding situations that require alterations in the regimen. Nursing will be well versed in administration and monitoring for side effects, particularly extravasation, and inform the team of any concerns.
Team coordination is also necessary when considering using dexrazoxane to decrease the risk of cardiotoxicity.
This type of interprofessional paradigm leads to the best patient result for anti-infective care with doxorubicin. [Level 5]
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