Adriamycin

Name: Adriamycin

Adriamycin Precautions

Adriamycin may cause serious side effects including:

  • Heart problems. Adriamycin may cause heart problems that may lead to death. These problems can happen during your treatment or months to years after stopping treatment. In some cases heart problems are irreversible. Your chance of heart problems is higher if you:
    • already have heart problems
    • have a history of radiation therapy or are currently receiving radiation therapy to your chest
    • have had treatment with certain other anti-cancer medicines
    • take other medicines that can affect your heart

Tell your doctor if you get any of these symptoms of heart problems:

  • shortness of breath
  • cough
  • swelling of your feet and ankles
  • fast heartbeat

Your doctor should do tests to check your heart before, during, and after your treatment with Adriamycin.

  • Secondary cancers. Some people who have received Adriamycin have developed acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Your chance of developing a secondary cancer is higher if you receive Adriamycin along with other anti-cancer medicines or with radiation therapy.
  • Decreased blood cell counts. Adriamycin can cause a severe decrease in neutrophils (a type of white blood cells important in fighting in bacterial infections), red blood cells (blood cells that carry oxygen to the tissues), and platelets (important for clotting and to control bleeding). Your doctor will check your blood cell count during your treatment with Adriamycin and after you have stopped your treatment.

Do not receive Adriamycin if:

  • your blood cell counts are too low: platelets (which help your blood to clot), red blood cells (which help to carry iron and oxygen throughout your body), and white blood cells (which help to fight infection)
  • you have a severe liver problem
  • you have had a recent heart attack or have severe heart problems
  • you have had previous treatment with Adriamycin or certain other anticancer medicines and received the maximum dose allowed
  • you are allergic to certain other anti-cancer medicines, Adriamycin hydrochloride, or any other ingredient in Adriamycin.

Talk to your doctor before receiving Adriamycin if you have any of the conditions listed above.

Avoid receiving live vaccines during treatment with Adriamycin. Talk to your doctor to find out which vaccines are safe for you while receiving Adriamycin.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your doxorubicin injection.

What should I avoid while taking Adriamycin (doxorubicin)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Do not receive a "live" vaccine while using doxorubicin, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Commonly used brand name(s)

In the U.S.

  • Adriamycin

Available Dosage Forms:

  • Powder for Solution
  • Solution

Therapeutic Class: Antineoplastic Agent

Chemical Class: Anthracycline

Uses of Adriamycin

  • It is used to treat cancer.

How do I store and/or throw out Adriamycin?

  • If you need to store Adriamycin at home, talk with your doctor, nurse, or pharmacist about how to store it.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Adriamycin or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Adriamycin. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Warnings and Precautions

Cardiomyopathy and Arrhythmias

Cardiomyopathy

Doxorubicin can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin. Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart failure (CHF). The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin, 3 to 5% at a dose of 400 mg/m2, 5 to 8% at a dose of 450 mg/m2, and 6 to 20% at a dose of 500 mg/m2, when doxorubicin is administered every 3 weeks. There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents such as cyclophosphamide and trastuzumab.

Pericarditis and myocarditis have also been reported during or following doxorubicin treatment.

Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of doxorubicin, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative dose exceeds 300 mg/m2 . Use the same method of assessment of LVEF at all time points [see Use in Specific Populations (8.4 )].

Consider the use of dexrazoxane to reduce the incidence and severity of cardiomyopathy due to doxorubicin administration in patients who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin.

Arrhythmias

Doxorubicin can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after doxorubicin administration and at any time point during treatment. Tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia may occur. Electrocardiographic changes including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur. These electrocardiographic changes may be transient and self-limited and may not require dose-modifications of doxorubicin.

Secondary Malignancies

The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin. Cumulative incidences ranged from 0.2% at five years to 1.5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer. These leukemias generally occur within 1 to 3 years of treatment.

Extravasation and Tissue Necrosis

Extravasation of doxorubicin can result in severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting. When given via a peripheral venous line, infuse doxorubicin over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. If signs or symptoms of extravasation occur, immediately terminate the injection or infusion [see Dosage and Administration (2.3)]. Extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of the infusion needle. If extravasation is suspected, apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days. If appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation.

Severe Myelosuppression

Doxorubicin can cause myelosuppression. In Study 1, the incidence of severe myelosuppression was: grade 4 leukopenia (0.3%), grade 3 leukopenia (3%), and grade 4 thrombocytopenia (0.1%). A dose-dependent, reversible neutropenia is the predominant manifestation of hematologic toxicity from doxorubicin. When doxorubicin is administered every 21 days, the neutrophil count reaches its nadir 10 to 14 days after administration with recovery usually occurring by the 21st day.

Obtain baseline assessment of blood counts and carefully monitor patients during treatment for possible clinical complications due to myelosuppression.

Use in Patients with Hepatic Impairment

The clearance of doxorubicin is decreased in patients with elevated serum bilirubin with an increased risk of toxicity [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Reduce the dose of doxorubicin in patients with serum bilirubin levels of 1.2 to 5.0 mg/dL [see Dosage and Administration (2.2)]. Doxorubicin is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Contraindications (4)]. Obtain liver tests including SGOT, SGPT, alkaline phosphatase, and bilirubin prior to and during doxorubicin therapy.

Tumor Lysis Syndrome

Doxorubicin may induce tumor lysis syndrome in patients with rapidly growing tumors. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome.

Radiation Sensitization and Radiation Recall

Doxorubicin can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive doxorubicin after prior radiation therapy.

Embryofetal Toxicity

Doxorubicin can cause fetal harm when administered to a pregnant woman. Doxorubicin was teratogenic and embryotoxic in rats and rabbits at doses lower than the recommended human dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus [see Use in Specific Populations (8.1)].

Advise female patients of reproductive potential to use highly effective contraception during treatment with doxorubicin and for 6 months after treatment. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking doxorubicin [see Use in Specific Populations (8.1) and (8.6 )].

Drug Interactions

Effect of CYP3A4 Inhibitors, Inducers and P-gp

Doxorubicin is a major substrate of cytochrome P450 CYP3A4 and CYP2D6, and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4, CYP2D6, and/or P-gp (e.g., verapamil), resulting in increased concentration and clinical effect of doxorubicin. Inducers of CYP3A4 (e.g., phenobarbital, phenytoin, St. John’s Wort) and P-gp inducers may decrease the concentration of doxorubicin. Avoid concurrent use of doxorubicin with inhibitors and inducers of CYP3A4, CYP2D6, or P-gp.

Trastuzumab

Concurrent use of trastuzumab and doxorubicin results in an increased risk of cardiac dysfunction. Avoid concurrent administration of doxorubicin and trastuzumab. The appropriate interval for administering doxorubicin following trastuzumab therapy has not been determined

[see Warnings and Precautions (5.1)].

Paclitaxel

Paclitaxel, when given prior to doxorubicin, increases the plasma-concentrations of doxorubicin and its metabolites. Administer doxorubicin prior to paclitaxel if used concomitantly.

Dexrazoxane

Do not administer dexrazoxane as a cardioprotectant at the initiation of doxorubicin containing chemotherapy regimens. In a randomized trial in women with metastatic breast cancer, initiation of dexrazoxane with doxorubicin based chemotherapy resulted in a significantly lower tumor response rate (48% vs. 63%; p=0.007) and shorter time to progression than in women who received doxorubicin based chemotherapy alone.

6-Mercaptopurine

Doxorubicin may potentiate 6-mercaptopurine-induced hepatotoxicity. In 11 patients with refractory leukemia treated with 6-mercaptopurine (500 mg/m2 intravenously daily for 5 days per cycle every 2 to 3 weeks) and doxorubicin (50 mg/m2 intravenous once per cycle every 2 to 3 weeks) alone or with vincristine and prednisone, all developed hepatic dysfunction manifested by elevations of total serum bilirubin, alkaline phosphatase and aspartate aminotransferase.

Clinical Studies

The clinical efficacy of doxorubicin containing regimens for the post-operative, adjuvant treatment of surgically resected breast cancer was evaluated in a meta-analysis conducted by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). The EBCTCG meta-analyses compared cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) to no chemotherapy (19 trials including 7523 patients) and doxorubicin containing regimens with CMF as an active control (6 trials including 3510 patients). Data from the meta-analysis of trials comparing CMF to no therapy were used to establish the historical treatment effect size for CMF regimens. The major efficacy outcome measures were disease-free survival (DFS) and overall survival (OS).

Of the 3510 women (2157 received doxorubicin containing regimens and 1353 received CMF treatment) with early breast cancer involving axillary lymph nodes included in the six trials from the meta-analyses, approximately 70% were premenopausal and 30% were postmenopausal. At the time of the meta-analysis, 1745 first recurrences and 1348 deaths had occurred. The analyses demonstrated that doxorubicin containing regimens retained at least 75% of the historical CMF adjuvant effect on DFS with a hazard ratio (HR) of 0.91 (95% CI, 0.8 to 1.01 ) and on OS with a HR of 0.91 (95% CI, 0.8 to 1.03 ). Results of these analyses for both DFS and OS are provided in Table 2 and Figures 1 and 2.

Table 2. Summary of Randomized Trials Comparing Doxorubicin Containing Regimens Versus CMF in Meta-Analysis

Study

(starting year)

Regimens

No. of Cycles

No. of Patients

Doxorubicin Containing Regimens vs. CMF HR** (95% CI)

DFS

OS

NSABP B-15

(1984)

AC

CMF

4

6

1562*

776

0.93 (0.82 to 1.06)

0.97 (0.83 to 1.12)

SECSG 2 (1976)

FAC

CMF

6

6

260

268

0.86 (0.66 to 1.13)

0.93 (0.69 to 1.26)

ONCOFRANCE (1978)

FACV

CMF

12

12

138

113

0.71 (0.49 to 1.03)

0.65 (0.44 to 0.96)

SE Sweden BCG A (1980)

AC

CMF

6

6

21

22

0.59 (0.22 to 1.61)

0.53 (0.21 to 1.37)

NSABC Israel Br0283 (1983)

AVbCMF†

CMF

4

6

6

55

50

0.91 (0.53 to 1.57)

0.88 (0.47 to 1.63)

Austrian BCSG 3 (1984)

CMFVA

CMF

6

8

121

124

1.07 (0.73 to 1.55)

0.93 (0.64 to 1.35)

Combined Studies

Doxorubicin Containing Regimens

CMF

2157

1353

0.91 (0.82 to 1.01)

0.91 (0.81 to 1.03)

 Abbreviations: DFS = disease free survival; OS = overall survival; AC = doxorubicin, cyclophosphamide; AVbCMF = doxorubicin, vinblastine, cyclophosphamide, methotrexate, 5-fluorouracil; CMF = cyclophosphamide, methotrexate, 5-fluorouracil; CMFVA = cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, doxorubicin; FAC = 5-fluorouracil, doxorubicin, cyclophosphamide; FACV = 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine; HR = hazard ratio; CI = confidence interval

* 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.
** a hazard ratio of less than 1 indicates that the treatment with doxorubicin containing regimens is associated
 with lower risk of disease recurrences or death compared to the treatment with CMF.

† Patients received alternating cycles of AVb and CMF.

For Healthcare Professionals

Applies to doxorubicin: compounding powder, intravenous powder for injection, intravenous solution

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 (the active ingredient contained in Adriamycin) 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.[Ref]

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.[Ref]

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 (the active ingredient contained in Adriamycin) 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.[Ref]

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.[Ref]

Dermatologic

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.[Ref]

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

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Hypersensitivity

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

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.[Ref]

Renal

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.[Ref]

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.[Ref]

Other

Radiation pneumonitis or esophagitis may be more likely with the combination of doxorubicin (the active ingredient contained in Adriamycin) 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.[Ref]

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.[Ref]

Oncologic

Oncologic side effects including secondary leukemia have been associated with prior exposure to doxorubicin (the active ingredient contained in Adriamycin) A single case of skin cancer that developed at the site of doxorubicin extravasation 10 years prior has also been reported.[Ref]

Ocular

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

Genitourinary

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

Musculoskeletal

Musculoskeletal side effects have been extremely rare. In one case, administration of doxorubicin (the active ingredient contained in Adriamycin) was associated with a clinically significant flare of ankylosing spondylitis.[Ref]

Some side effects of Adriamycin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Doxorubicin Pregnancy Warnings

Doxorubicin has been assigned to pregnancy category D by the FDA. Animal studies have revealed evidence of embryotoxicity and teratogenicity. Although controlled data from human pregnancy studies are not available, several cases of birth defects have been associated with the use of doxorubicin. Some experts feel that the use of doxorubicin for the treatment of breast cancer during pregnancy improves the high postpartum maternal mortality rate and the chance of producing live births without excessive risk to the fetus or the mother, even if administered early in the course of pregnancy. Doxorubicin should only be given during pregnancy when there are no alternatives and benefit outweighs risk.

Doxorubicin crosses the human placenta. Several cases of birth defects have been associated with the use of doxorubicin during pregnancy. These birth defects have included imperforate anus, rectovaginal fistula, brachycephaly, hypoplasia of the anterior cranial base and face, synostoses of cranial sutures, hypoplastic digits, and fetal maceration. Fetal death has been reported 36 hours after treatment with doxorubicin and other neoplastic agents. Doxorubicin may cause reversible testicular and ovarian dysfunction or menstrual abnormalities. Most men who have received doxorubicin regain spermatogenesis and sperm motility. Some women who were previously treated with doxorubicin have subsequently had normal pregnancies. Development of sterility may depend on the dose, duration of therapy, and the pretreatment state of gonadal function. Pregnancy outcome in women who received doxorubicin for malignancy in childhood has been reported to generally be favorable. Those with baseline left ventricular dysfunction should be considered at increased risk for worse pregnancy outcome and further deterioration in myocardial function. Peripartum heart failure has been reported years after doxorubicin therapy. Pregnancy, preeclampsia, anemia, or overhydration are possible precipitating factors in the emergence of heart failure in patients who have received doxorubicin. While there are no data regarding the handling of doxorubicin or other cytotoxic agents by women who are pregnant, attempting to conceive, or breast-feeding, some experts suggest the need for caution.

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