"The U.S. Food and Drug Administration today approved Kadcyla (ado-trastuzumab emtansine), a new therapy for patients with HER2-positive, late-stage (metastatic) breast cancer.
HER2 is a protein involved in normal cell growth. It is foun"...
Ellence Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Ellence (epirubicin hydrochloride) is used to treat breast cancer. It is a cancer (antineoplastic) medication. This medication is available in generic form. Common side effects include nausea/vomiting (may be severe), diarrhea, abdominal pain, flushing, or skin/nail color changes.
The recommended dose of Ellence is 100 to 120 mg/mē, administered by intravenous infusion, given in repeated 3- to 4-week cycles. The total dose may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle. Ellence may interact with paclitaxel, docetaxel, cimetidine, or calcium channel blockers. Tell your doctor all medications and supplements you use. Ellence is not recommended for use during pregnancy. It may harm a fetus. If you become pregnant or think you may be pregnant, tell your doctor. Males and females using this drug should use birth control (e.g., birth control pills, condoms) during treatment; consult your doctor. It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended.
Our Ellence (epirubicin hydrochloride) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Ellence in Detail - Patient Information: Side Effects
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect such as:
- feeling short of breath, even with mild exertion;
- swelling, rapid weight gain;
- severe burning, stinging, pain, swelling, redness, or skin changes around the IV needle;
- white patches or sores inside your mouth or on your lips;
- severe vomiting, thirst, and hot dry skin;
- fever, chills, body aches, flu symptoms, or signs of infection;
- slow or uneven heart rate, weak pulse;
- confusion, fainting;
- muscle weakness, tingly feeling;
- urinating less than usual or not at all; or
- easy bruising or bleeding, unusual weakness.
Less serious side effects may include:
- red colored urine for 1 or 2 days after receiving the medication;
- nausea, vomiting, diarrhea;
- tired feeling;
- hair loss;
- changes in your menstrual periods;
- warmth, redness, or tingly feeling under your skin;
- darkening of your skin or nails; or
- mild itching or skin rash.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Ellence (Epirubicin hydrochloride) »
What is Patient Information Overview?
A concise overview of the drug for the patient or caregiver from First DataBank.
Ellence Overview - Patient Information: Side Effects
Nausea, vomiting, diarrhea, abdominal pain, flushing, or skin/nail color changes may occur. Nausea and vomiting can be severe. In some cases, your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating before treatment, or limiting activity may help lessen some of these effects. If these effects persist or worsen, tell your doctor or pharmacist promptly.
This medication may cause your urine to turn a reddish color. This is a normal, harmless effect of the drug that usually stops within 2 days after each dose and should not be mistaken for blood in your urine.
Temporary hair loss is a common side effect. Normal hair growth should return after treatment has ended.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including: menstrual changes (e.g., stopped periods), unusual bleeding/bruising (e.g., small red spots on the skin, black/bloody stools, bloody urine, vomit that looks like coffee grounds).
Pain or sores in the mouth and throat may occur. Brush your teeth gently/carefully, avoid using mouthwash that contains alcohol, and rinse your mouth frequently with cool water mixed with baking soda or salt. It may also be best to eat soft, moist foods.
Severe nausea, vomiting, and diarrhea may infrequently result in a loss of too much body water (dehydration). Contact your doctor promptly if you notice any symptoms of dehydration such as unusual decreased urination, unusual dry mouth/increased thirst, lack of tears, dizziness/lightheadedness, or pale/wrinkled skin.
Get medical help right away if you have any very serious side effects, including: chest pain, coughing up blood, sudden pain/swelling/redness usually in the leg.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), trouble breathing, severe dizziness.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Read the entire patient information overview for Ellence (Epirubicin hydrochloride)»
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Ellence FDA Prescribing Information: Side Effects
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Integrated safety data are available from two studies (Studies MA-5 and GFEA-05) [see Clinical Studies] evaluating ELLENCE-containing combination regimens in patients with early breast cancer. Of the 1260 patients treated in these studies, 620 patients received the higher-dose ELLENCE regimen (FEC-100/CEF-120), 280 patients received the lower-dose ELLENCE regimen (FEC-50), and 360 patients received CMF. Serotonin-specific antiemetic therapy and colony-stimulating factors were not used in these trials. Clinically relevant acute adverse events are summarized in Table 1.
Table 1: Clinically Relevant
Acute Adverse Events in Patients with Early Breast Cancer
|Event||% of Patients|
|FEC-100/CEF-120 (N=620)||FEC-50 (N=280)||CMF (N=360)|
|Grades 1-4||Grades 3/4||Grades 1-4||Grades 3/4||Grades 1-4||Grades 3/4|
|Body as a Whole|
|FEC & CEF = cyclophosphamide + ELLENCE + fluorouracil; CMF = cyclophosphamide + methotrexate + fluorouracil; NA = not available Grade 1 or 2 changes in transaminase levels were observed but were more frequently seen with CMF than with CEF.|
Table 2 describes the incidence of delayed adverse events in patients participating in the MA-5 and GFEA-05 trials.
Table 2: Long-Term Adverse
Events in Patients with Early Breast Cancer
|Event||% of Patients|
|Asymptomatic drops in LVEF||2.1*||1.4||0.8*|
|*In study MA-5, cardiac function was not monitored after 5 years. Two cases of acute lymphoid leukemia (ALL) were also observed in patients receiving ELLENCE. However, an association between anthracyclines such as ELLENCE and ALL has not been clearly established.|
Overview of Acute and Delayed Toxicities
Dose-dependent, reversible leukopenia and/or neutropenia is the predominant manifestation of hematologic toxicity associated with ELLENCE and represents the most common acute dose-limiting toxicity of this drug. In most cases, the white blood cell (WBC) nadir is reached 10 to 14 days from drug administration. Leukopenia/neutropenia is usually transient, with WBC and neutrophil counts generally returning to normal values by Day 21 after drug administration. As with other cytotoxic agents, ELLENCE at the recommended dose in combination with cyclophosphamide and fluorouracil can produce severe leukopenia and neutropenia. Severe thrombocytopenia and anemia may also occur. Clinical consequences of severe myelosuppression include fever, infection, septicemia, septic shock, hemorrhage, tissue hypoxia, symptomatic anemia, or death. If myelosuppressive complications occur, use appropriate supportive measures (e.g., intravenous antibiotics, colony-stimulating factors, transfusions). Myelosuppression requires careful monitoring. Assess total and differential WBC, red blood cell (RBC), and platelet counts before and during each cycle of therapy with ELLENCE [see WARNINGS AND PRECAUTIONS].
A dose-dependent mucositis (mainly oral stomatitis, less often esophagitis) may occur in patients treated with ELLENCE. Clinical manifestations of mucositis may include a pain or burning sensation, erythema, erosions, ulcerations, bleeding, or infections. Mucositis generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations; most patients recover from this adverse event by the third week of therapy. Hyperpigmentation of the oral mucosa may also occur. Nausea, vomiting, and occasionally diarrhea and abdominal pain can also occur. Severe vomiting and diarrhea may produce dehydration. Antiemetics may reduce nausea and vomiting; consider prophylactic use of antiemetics before therapy [see WARNINGS AND PRECAUTIONS].
Cutaneous and Hypersensitivity Reactions
Alopecia occurs frequently, but is usually reversible, with hair regrowth occurring within 2 to 3 months from the termination of therapy. Flushes, skin and nail hyperpigmentation, photosensitivity, and hypersensitivity to irradiated skin (radiation-recall reaction) have been observed. Urticaria and anaphylaxis have been reported in patients treated with ELLENCE; signs and symptoms of these reactions may vary from skin rash and pruritus to fever, chills, and shock.
In a retrospective survey, including 9144 patients, mostly with solid tumors in advanced stages, the probability of developing CHF increased with increasing cumulative doses of ELLENCE (Figure 1). The estimated risk of ELLENCE-treated patients developing clinically evident CHF was 0.9% at a cumulative dose of 550 mg/m², 1.6% at 700 mg/m², and 3.3% at 900 mg/m². The risk of developing CHF in the absence of other cardiac risk factors increased steeply after an ELLENCE cumulative dose of 900 mg/m² [see WARNINGS AND PRECAUTIONS].
Figure 1: Risk of CHF in
9144 Patients Treated with ELLENCE
In another retrospective survey of 469 ELLENCE-treated patients with metastatic or early breast cancer, the reported risk of CHF was comparable to that observed in the larger study of over 9000 patients [see WARNINGS AND PRECAUTIONS].
Other serious drug-related cardiovascular adverse events that occurred during clinical trials with ELLENCE, administered in different indications, include ventricular tachycardia, AV block, bundle branch block, bradycardia and thromboembolism.
An analysis of 7110 patients who received adjuvant treatment with ELLENCE in controlled clinical trials as a component of poly-chemotherapy regimens for early breast cancer, showed a cumulative risk of secondary acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) of about 0.27% (approximate 95% CI, 0.14-0.40) at 3 years, 0.46% (approximate 95% CI, 0.28-0.65) at 5 years, and 0.55% (approximate 95% CI, 0.33-0.78) at 8 years. The risk of developing AML/MDS increased with increasing ELLENCE cumulative doses as shown in Figure 2.
Figure 2: Risk of AML/MDS in
7110 Patients Treated with ELLENCE
The cumulative probability of developing AML/MDS was found to be particularly increased in patients who received more than the maximum recommended cumulative dose of ELLENCE (720 mg/m²) or cyclophosphamide (6,300 mg/m²), as shown in Table 3.
Table 3: Cumulative
Probability of AML/MDS in Relation to Cumulative Doses of ELLENCE and
|Years from Treatment Start||Cumulative Probability of Developing AML/MDS % (95% CI)|
|Cyclophosphamide Cumulative Dose ≤ 6,300 mg/m²||Cyclophosphamide Cumulative Dose > 6,300 mg/m²|
|ELLENCE Cumulative Dose ≤ 720 mg/m²
|ELLENCE Cumulative Dose > 720 mg/m²
|ELLENCE Cumulative Dose ≤ 720 mg/m²
|ELLENCE Cumulative Dose > 720 mg/m²
|3||0.12 (0.01-0.22)||0.00 (0.00-0.00)||0.12 (0.00-0.37)||4.37 (1.69-7.05)|
|5||0.25 (0.08-0.42)||2.38 (0.00-6.99)||0.31 (0.00-0.75)||4.97 (2.06-7.87)|
|8||0.37 (0.13-0.61)||2.38 (0.00-6.99)||0.31 (0.00-0.75)||4.97 (2.06-7.87)|
Injection-Site Reactions [see WARNINGS AND PRECAUTIONS].
The following adverse reactions have been identified during post-approval use of ELLENCE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders: anaphylaxis
Metabolism and nutrition disorders: dehydration, hyperuricemia
Respiratory, thoracic and mediastinal disorders: pulmonary embolism
Gastrointestinal disorders: erosions, ulcerations, pain or burning sensation, bleeding, hyperpigmentation of the oral mucosa
Skin and subcutaneous tissue disorders: erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction), urticaria
Renal and urinary disorders: red coloration of urine for 1 to 2 days after administration
General disorders and administration site conditions: fever, chills Injury, poisoning and procedural complications: chemical cystitis (following intravesical administration)
Read the entire FDA prescribing information for Ellence (Epirubicin hydrochloride) »
Additional Ellence Information
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