Editor's note: This article was first published on April 10, 2015, and updated on May 29, 2018.

Learn even more about the red devil on Episode 92 of the Oncology Nursing Podcast.

Doxorubicin (Adriamycin®) is a cytotoxic chemotherapy drug and an antitumor antibiotic in the anthracycline group. Isolated from cultures of Streptomyces peucetius var. caesius (soil fungus), doxorubicin is semi-synthetically produced and is indicated for the treatment of a multitude of cancers, including breast and ovarian, leukemia (acute myelogenous leukemia [AML] and acute lymphoblastic leukemia), Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumor, neuoroblastoma, and sarcoma. As you can imagine, with all of those indications, you’ll be seeing this drug quite a lot. Most commonly, you’ll use it to treat patients with breast cancer.

So let’s start with the most talked about and memorable characteristic of this drug—it's color. Doxorubicin is bright red—seriously red. In fact, it will likely get the attention not only of the patient receiving it but also of the other patients in the room, particularly if they’re not receiving the same drug. Upon first glance, most nurses think, “Well, it’s pretty.” And it is. It is a pretty color and a pretty nasty little chemotherapy agent. As such, it deservedly has been nicknamed the red devil.

Administration schedules may vary depending on the diagnosis being treated with regard to the number and frequency of cycles. For example, in breast cancer, four cycles is typical. This can be given every three weeks or every two weeks (considered dose dense) if a granulocyte-macrophage colony-stimulating factor is added for support. For lymphomas, in the combo of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone), the frequency and number of cycles will be different. Doxorubicin can be administered as a continuous infusion (protect from light); however, in the outpatient setting, you will typically give this as a bolus injection.

I cannot help my childhood memory conjuring up an image of the red Kool-Aid man busting through a wall and running through my patient's vein as I push doxorubicin. "Oh, Yeah!" Quite notably, doxorubicin is a vesicant. While I am exceedingly grateful to have never seen an extravasation in one of my own patients, I have seen a plethora of horrific pictures documenting the significant tissue damage this drug can cause if given the opportunity. Needless to say, I have always had and still keep a healthy respect for this chemotherapy agent.

Check your institutional policy for specifics, but blood return should be checked throughout your slow IV push (over 3–10 minutes). If you see red streaking or a flare-type reaction along the vein of infusion or facial flushing, you can slow down the push. However, keep in mind that lengthening the time of administration beyond 10 minutes increases the risk of extravasation.   

Because of its nasty reputation as a vesicant, most patients will get a port-a-cath. However, this does not completely eliminate the risk of extravasation. Patients can incur tissue damage if there is a tear in the central line or a misplaced or dislodged needle. Whether you use a port or peripheral line, instruct your patients to immediately report any pain, burning, or redness around the site during the infusion and even after they've returned home. As with a peripheral line, check for blood return throughout administration via port or other central line. Do not administer doxorubicin without a good blood return. You may need to start a new line peripherally, or in the case of a port, investigate further to be certain there are no issues with placement. Again, know your institution's practice as some may have standing orders and a protocol for such instances. The ONS/American Society of Clinical Oncology Chemotherapy Safety Standards indicate that each institution should have extravasation management procedures outline and antidotes within easy access.

If extravasation occurs, stop immediately and apply dry, cold compresses for 20 minutes, four times daily, for one to two days. Avoid applying pressure to the site, and if the extravasation is in an extremity, elevate it. Blistering, ulceration, and persistent pain may be indications for wide excision surgery of the damaged tissue followed by skin grafting. (Feel that healthy respect developing?) Dexrazoxane hydrochloride is now U.S. Food and Drug Administration approved to treat anthracycline extravasations, and topical dimethyl sulfoxide may be used for extravasation of doxorubicin when dexrazoxane is not available.

Like many chemotherapy drugs, doxorubicin is usually given in combination with one or more agents. For breast cancer, it's typically given with cyclophosphamide. For lymphomas and leukemias, it is combined with even more drugs to make regimens like CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone), R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone), and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine).

Beyond the earnest concern about this drug's vesicant properties, doxorubicin's side effects also contribute to its red devil status. Common side effects (greater than 30%) include nausea and vomiting, low blood counts (red blood cells, white blood cells, and platelet count), with the nadir being around 10 days, mouth sores, and alopecia. This chemotherapy agent is considered to have moderate (30%–60%) emetogenic potential, and based on my personal experience, I would say it's on the high end of that spectrum. Be sure to premedicate appropriately and ensure that the patient has adequate antinausea medicines at home (I advise my patients to always have at least two different options at home). Review a plan to prevent and manage nausea and vomiting with your patients and write down instructions for taking nausea medications.

As for preventing mouth sores, encourage patients to initiate an oral care protocol that focuses on good oral hygiene, use of a soft toothbrush, avoiding alcohol-based mouthwashes, and rinsing their mouths with a mixture of baking soda and salt with warm water multiple times per day. The National Cancer Institute recommends mixing one cup of warm water with 1/4 teaspoon baking soda and 1/8 teaspoon salt. Swish rinse around in mouth, spit, then rinse with plain water and repeat every three hours during the day. Other protocols use 1/2 teaspoon each of salt and baking soda with one cup of warm water. Check with your institution and adhere to your practice's standards. The key with any oral care protocol is consistent use.

Although not evidenced-based (I know, purely anecdotal, but I feel obligated to mention), throughout my nursing experience in various settings, I have found camps of believers and non-believers regarding the use of cryotherapy with doxorubicin administration. I originally practiced in groups of the strong believers camp. We did cryotherapy with every doxorubicin push. I have to admit, we had a remarkably low incidence of mucositis in those patients. Was that just luck? I don't know, maybe.

When I moved to a new state and began practicing in another outpatient institution, I was the only one who did cryotherapy with doxorubicin. People asked me why I did it. "Because it works" was always my response. Again, I have not found cryotherapy with average dose doxorubicin listed in any evidence-based practice. Nevertheless, I stand by my nursing experience (for whatever that's worth!). Regardless of whether you believe it, if you have a patient who experiences mouth sores after the first cycle of doxorubicin, remember that cryotherapy is a free, easy intervention (and it can't hurt to try it) for future cycles, although some institutions may require a provider order. (Let the comments fly on which camp you belong to!)

Another important thing to mention to your patient is that because of doxorubicin's bright red color, their urine will be discolored for generally one to two days after treatment. This may appear as a range of red, pink, orange, or brownish colored urine, which is all normal. Any discoloration should be obviously different than the appearance of frank hematuria. Less common symptoms include watery eyes, darkening of nails, infertility, and radiation recall (redness/darkening of skin over previously radiated area).

A serious but uncommon side effect of doxorubicin can be irreversible heart damage. This includes arrhythmias, EKG changes, angina, myocardial infarction, and cardiomyopathy, which manifests as a reduction in left ventricular ejection fraction (LVEF) and/or symptoms of congestive heart failure. Because of the potential of cardiotoxicity, you can receive only up to a certain amount of doxorubicin during your lifetime. The lifetime maximum dose (450–550 mg/m2) may be lower if you have heart disease risk factors such as radiation to the chest, advancing age, and use of other heart-toxic drugs (such as cyclophophamide and/or trastuzumab).

Every patient should have a multigated acquisition scan or echocardiogram to evaluate a baseline LVEF prior to initiating treatment. Cardiac symptoms should be monitored closely during treatment and after completion because problems can occur as late as seven to eight years after the last dose. In addition, the risk of developing a secondary malignancy, AML, and myelodysplastic syndrome is increased following treatment with doxorubicin. These leukemias generally occur within one to three years of treatment.

In summary, doxorubicin is a very useful chemotherapy drug used in a multitude of diagnoses and is commonly seen in the outpatient setting for the treatment of breast cancer, lymphomas, and leukemias. This agent has earned its infamous nickname, the red devil, based on its bright red (Kool-Aid red) color, vesicant properties, and side-effect profile, including hair loss, myelosuppression, nausea and vomiting, mouth sores, and rare but serious cardiotoxicity. It requires vigilant monitoring particularly during the slow IV bolus administration. Infusion nurses should check their institution's standard practice regarding checking for blood return throughout administration as well as the protocol if a blood return is absent.