Doxorubicin Side Effects

Brand Names: Adriamycin, Rubex

Please note - some side effects for Doxorubicin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Doxorubicin - for the Consumer

Doxorubicin Liposomal

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Doxorubicin Liposomal:

Constipation; diarrhea; hair loss; indigestion; loss of appetite; nausea; tiredness; weakness; weight changes.

Seek medical attention right away if any of these SEVERE side effects occur when using Doxorubicin Liposomal:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest or throat; swelling of the mouth, face, lips, or tongue); absence of menstrual cycle or menstrual changes; back pain; black, tarry stools; bluish skin or nails; calf or leg pain, swelling, redness, or tenderness; chest pain; dizziness or light-headedness; fainting; fast, slow, or irregular heartbeat; flushing; headache; loose or bloody stools; pain, redness, burning, stinging, swelling, or open sores at the injection site; rectal bleeding or irritation; redness or discharge of the eyes; redness, pain, swelling, peeling, tingling, or blistering of the palms of the hands and the soles of the feet; severe or persistent nausea; shortness of breath; sudden, unexplained weight gain; swelling of the hands, ankles, or feet; swelling or soreness of the mouth or tongue; symptoms of dehydration (eg, dry mouth or eyes, decreased urination, fast heartbeat, sluggishness, unusual thirst); symptoms of infection (eg, fever, chills, cough, sore throat, burning or painful urination); unusual bruising or bleeding; unusual tiredness or weakness; vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Doxorubicin

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Doxorubicin:

Diarrhea; hair loss; loss of appetite; nausea; stomach pain; tiredness; weakness; weight changes.

Seek medical attention right away if any of these SEVERE side effects occur when using Doxorubicin:

Severe allergic reactions (rash; hives; itching; difficulty breathing; dizziness; flushed face; tightness in the chest; swelling of the mouth, face, lips, or tongue); absence of menstrual cycle; black, tarry stools; chest pain; fainting; fast, slow, or irregular heartbeat; headache; loose or bloody stools; pain, redness, burning, stinging, swelling, or open sores at the injection site; rectal bleeding or irritation; redness or discharge of the eyes; redness, pain, swelling, peeling, tingling, or blistering of the palms of the hands and the soles of the feet; severe or persistent nausea or vomiting; shortness of breath; sudden, unexplained weight gain; swelling of the hands, ankles, or feet; swelling or soreness of the mouth or tongue; symptoms of dehydration (eg, dry mouth or eyes, decreased urination, fast heartbeat, sluggishness, unusual thirst); symptoms of infection (eg, fever, chills, cough, sore throat, burning or painful urination); unusual bruising or bleeding; unusual tiredness or weakness; vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

Doxorubicin Side Effects - for the Professional

Doxorubicin

Dose limiting toxicities of therapy are myelosuppression and cardiotoxicity. Other reactions reported are:

Cardiotoxicity

.

Cutaneous

Reversible complete alopecia occurs in most cases. Hyperpigmentation of nailbeds and dermal creases, primarily in pediatric patients, and onycholysis have been reported in a few cases. Radiation recall reaction has occurred with Doxorubicin administration. Rash, itching, or photosensitivity may occur.

Gastrointestinal

Acute nausea and vomiting occurs frequently and may be severe. This may be alleviated by antiemetic therapy. Mucositis (stomatitis and esophagitis) may occur within 5 to 10 days of beginning therapy, and most patients recover from this adverse event within another 5 to 10 days. The effect may be severe, leading to ulceration and represents a site of origin for severe infections. The dosage regimen consisting of administration of Doxorubicin on three successive days results in greater incidence and severity of mucositis. Ulceration and necrosis of the colon, especially the cecum, may occur, leading to bleeding or severe infections which can be fatal. This reaction has been reported in patients with acute non-lymphocytic leukemia treated with a 3 day course of Doxorubicin combined with cytarabine. Anorexia, abdominal pain, dehydration, diarrhea, and hyperpigmentation of the oral mucosa have been occasionally reported.

Hematologic

.

Hypersensitivity

Fever, chills, and urticaria have been reported occasionally. Anaphylaxis may occur. A case of apparent cross sensitivity to lincomycin has been reported.

Neurological

Peripheral neurotoxicity in the form of local-regional sensory and/or motor disturbances have been reported in patients treated intra-arterially with Doxorubicin, mostly in combination with cisplatin. Animal studies have demonstrated seizures and coma in rodents and dogs treated with intra-carotid Doxorubicin. Seizures and coma have been reported in patients treated with Doxorubicin in combination with cisplatin or vincristine.

Ocular

Conjunctivitis, keratitis, and lacrimation occur rarely.

Other

Malaise/asthenia have been reported.

Adverse Reactions in Patients with Early Breast Cancer Receiving Doxorubicin-Containing Adjuvant Therapy

Safety data were collected from approximately 2300 women who participated in a randomized, open-label trial (NSABP B-15) evaluating the use of AC versus CMF in the treatment of early breast cancer involving axillary lymph nodes. In the safety analysis, the follow-up data from all patients receiving AC were combined (N = 1492 evaluable patients) and compared with data from patients receiving conventional CMF (i.e., oral cyclophosphamide; N = 739 evaluable patients). The most relevant adverse events reported in this study are provided in Table 2.

Table 2. Relevant Adverse Events in Patients with Early Breast Cancer Involving Axillary Lymph Nodes

	AC* N = 1492	Conventional CMF N = 739
* Includes pooled data from patients who received either AC alone for 4 cycles, or who were treated with AC for 4 cycles followed by 3 cycles of CMF
Treatment Administration
Mean number of cycles	3.8	5.5
Total Cycles	5676	4068
Adverse Events, % of Patients
Leukopenia
Grade 3 (1,000 to 1,999/mm3)	3.4	9.4
Grade 4 (< 1,000/mm3)	0.3	0.3
Thrombocytopenia
Grade 3 (25,000 to 49,999/mm3)	0	0.3
Grade 4 (< 25,000/mm3)	0.1	0
Shock, Sepsis	1.5	0.9
Systemic Infection	2.4	1.2
Nausea and Vomiting
Nausea only	15.5	42.8
Vomiting ≤ 12 hours	34.4	25.2
Vomiting > 12 hours	36.8	12
Intractable	4.7	1.6
Alopecia	92.4	71.4
Partial	22.9	56.3
Complete	69.5	15.1
Weight loss
5 to 10%	6.2	5.7
> 10%	2.4	2.8
Weight Gain
5 to 10%	10.6	27.9
> 10%	3.8	14.3
Cardiac Function
Asymptomatic	0.2	0.1
Transient	0.1	0
Symptomatic	0.1	0
Treatment-Related Death	0	0

Top

Side Effects by Body System - for Healthcare Professionals

Cardiovascular

The risk of heart failure is significantly increased after total doses of 550 mg/m2 (350 to 400 mg/m2 if there is history of prior radiation therapy which included the heart or the area around it or use of other potentially cardiotoxic agents, such as cyclophosphamide). Doxorubicin-induced heart failure can present one month to one year or more after termination of therapy. It is increasingly common to note LATE cardiomyopathy, especially in patients who received doxorubicin as a child or adolescent. Prevention has focused on cumulative dose limitation, earlier diagnosis (radionuclide angiocardiography or echocardiography), alterations in the schedule of administration (substitution of prolonged, continuous IV infusion for bolus injection), the development of less cardiotoxic anthracyclines, and use of cardioprotectors (dexrazoxane).

Treatment of doxorubicin-induced heart failure consists of traditional therapy with rest, digitalis, diuretics, and/or angiotensin converting enzyme (ACE) inhibitors as indicated.

While there has not been a reliable marker to predict which patients will develop doxorubicin-induced heart failure, serial non-invasive testing of LV function (radionuclide angiocardiography is usually more accurate than echocardiography) is strongly recommended (ECG has limited value). Recent data suggest plasma endothelin-1 and/or atrial natriuretic peptide levels may be useful for predicting the risk of cardiotoxicity associated with this drug. Endomyocardial biopsy permits a definitive evaluation of risk, but is invasive, expensive, and potentially risky. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight have all reported as risk factors for the development of cardiomyopathy.

Limited animal data suggest vitamins A and E, adenosine, coenzyme Q, N-acetylcysteine, and methylene blue may reduce the incidence of doxorubicin-induced cardiotoxicity. Other animal data has suggested that suitable antagonists of calcium-dependent pore formation such as cyclosporine A or tacrolimus may improve heart tolerance to doxorubicin.

The benefits of doxorubicin must be carefully weighed against the risks in patients with a demonstrable decrease in cardiac function.

Cardiovascular side effects have included congestive heart failure due to the development of left ventricular (LV) systolic dysfunction in 1% to 2% of patients. Retrospective data have shown that the incidence of clinical heart failure in patients with preexisting LV systolic dysfunction (ejection fraction [LVEF] < 50%), who experienced a decline of 10% or more in absolute LVEF, and who received at least 450 mg/m2 cumulative dose, is approximately 16%. (Data have shown right ventricular septal wall motion may also be affected and that LV diastolic dysfunction may precede the development of doxorubicin-induced LV systolic dysfunction.)

Early effects of anthracyclines also include extremely rare cases of pericarditis-myocarditis (which can affect patients with no prior history of cardiac disease and which carries a high mortality rate of about 20%), left ventricular dysfunction (which may lead to clinically significant heart failure in patients with limited cardiac reserve), and arrhythmias, the most common of which is sinus tachycardia. Although rhythm disturbances are common after acute administration they are rarely of clinical importance. Isolated cases of symptomatic supraventricular tachycardia, heart block, and ventricular arrhythmias (some sudden and fatal) have also been reported.

Hematologic

The leukocyte count usually reaches a nadir at 10 to 14 days after treatment.

Severe and/or persistent myelosuppression may result in superinfection and/or hemorrhage. GCSF has been used clinically to avoid dose reductions or interruptions in dose schedules.

A single case of acute hemolytic anemia has been reported after the administration of doxorubicin to a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This drug generates reactive oxygen compounds and methemoglobin in normal human red blood cells (RBCs) in vitro. In RBCs deficient in G6PD doxorubicin probably poses a potent oxidant stress. Thus patients with G6PD might be susceptible to hemolysis after receiving doxorubicin.

Hematologic side effects have been reported in 60% to 80% of patients and they may be profound (depending entirely on dose). While myelosuppression can affect all cell lines, leukopenia is most common, appearing in 60% to 75% of all treated patients. Absolute white blood cell counts of less than 1,000/mm3 are not uncommon after recommended therapeutic doses.

Dermatologic

A scalp tourniquet and/or scalp cooling may prevent doxorubicin-induced alopecia.

Dermatologic side effects have included reversible alopecia (scalp, pubis, and/or axilla). Less commonly, hyperpigmentation of nailbeds and dermal creases and oncholysis (nail loss) have been reported.

Gastrointestinal

Nausea and vomiting are preventable with appropriate antiemetic therapy.

Stomatitis or other ulcerations typically occur 2 to 10 days after administration and, if severe, can be complicated by bleeding or local infection. Severe cases of colonic ulceration can be fatal.

Gastrointestinal side effects have included acute nausea and vomiting in 20% to 85% of patients. Stomatitis has been reported in up to 80% of patients, and is dose and schedule-related. Ulceration of the esophagus and the colon (particularly the cecum) have also been reported. Anorexia and diarrhea have been reported in approximately 15% of patients. Rare cases of tongue hyperpigmentation have also been associated with the use of doxorubicin.

Local

Local side effects have included IV site problems such as phlebosclerosis (especially when a single vein and/or a small vein is used) and extravasation tissue necrosis.

Extravasation may occur with or without accompanying stinging or burning even if there is good blood return on aspiration of the infusion needle. If there are signs or symptoms of extravasation, the injection or infusion should be immediately terminated. If further therapy is necessary, an injection or infusion may be restarted in another vein and the affected area should be immediately treated. Many treatments have been proposed to slow or heal doxorubicin extravasation ulcers. The standard of care is ice packs for 24 hours for acute extravasation injury; some advocate topical application of 10% to 99% dimethyl sulfoxide (DMSO) with ice packs. However, because of the inconsistent results associated with some of these therapies and the progressive nature of extravasation reactions, plastic surgery consultation is generally recommended.

Hypersensitivity

Hypersensitivity reactions have occasionally been reported, and may include fever, chills, urticaria, angioneurotic edema or anaphylaxis.

Local IV site "flares" can be confused with extravasation, but are probably due to allergy to this drug. Flare reactions were reported in 3% to 18% of patients, but are now rare since the vehicle in which doxorubicin is carried has changed. Antiemetic therapy, antihistamines, and/or corticosteroids can decrease the risk of flares.

Flare reactions may be differentiated from extravasation. Flare reactions are characterized by erythema, appear proximally along the affected vein, and typically resolve within 45 minutes. Pain, burning and adverse sequelae are infrequent or absent. Extravasation, on the other hand, appears at the injection site and resolves slowly over days to weeks. As opposed to flare reactions, pain, burning, and edema are common, and adverse sequelae are variable and may be serious.

Allergic reactions have also been reported after the intravesical administration of doxorubicin.

Renal

Renal insufficiency has been associated with doxorubicin-induced hyperuricemia (secondary to cell lysis). Adequate hydration, diuresis, and allopurinol can be preventative.

Animal data suggest that doxorubicin may cause glomerular basement membrane injury via production of reactive oxygen species. Administration of some antioxidants, however, have failed to reduce the urinary excretion of lysozyme and N-acetyl-glucosaminidase (markers of tubule injury) in treated animals.

Renal side effects have included rare cases of new or worsened renal insufficiency. A single case of rapidly progressive glomerulonephritis without evidence of a secondary cause or immunologic mechanism has been reported.

Other

Radiation pneumonitis or esophagitis may be more likely with the combination of doxorubicin and XRT than with XRT alone. Prior XRT to the heart/mediastinum also increases the risk of doxorubicin-induced cardiomyopathy.

Endomyocardial biopsy data have demonstrated that the cellular morphological changes in patients who received doxorubicin and who were previously treated with cardiac or mediastinal XRT are markedly different and more severe than in treated patients without a history of cardiac or mediastinal XRT. Prior cardiac or mediastinal XRT appears to portend a higher risk of doxorubicin-induced cardiomyopathy.

Other side effects of doxorubicin have included the predisposition of patients who have previously received radiation therapy (XRT) to demonstrate the so-called "recall" phenomenon.

Oncologic

Oncologic side effects including secondary leukemia have been associated with prior exposure to doxorubicin. A single case of skin cancer that developed at the site of doxorubicin extravasation 10 years prior has also been reported.

Ocular

Ocular side effects have included rare cases of conjunctivitis, periorbital edema, lacrimation, blepharospasm, keratitis, and decreased visual acuity.

Genitourinary

Genitourinary side effects including rare cases of bladder contracture have been reported.

Musculoskeletal

Musculoskeletal side effects have been extremely rare. In one case, administration of doxorubicin was associated with a clinically significant flare of ankylosing spondylitis.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.