Myocardial damage, including acute left ventricular failure, can occur with epirubicin. The risk of cardiomyopathy is proportional to the cumulative exposure, with incidence rates from 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 cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction before and regularly during and after treatment with epirubicin.
Secondary acute myeloid leukemia and myelodysplastic syndrome occur at a higher incidence in patients treated with anthracyclines, including epirubicin.
Extravasation of epirubicin may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area.
Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur.
Note: Patients receiving 120 mg/m2/cycle IV as part of combination therapy (CEF-120 regimen) should receive prophylactic antibiotic therapy. Lower IV starting doses may be necessary for heavily pretreated patients, patients with preexisting myelosuppression, or with bone marrow involvement. If clinically reasonable, delay epirubicin therapy until other cardiotoxic agents with long half-lives (eg, trastuzumab) have been cleared. A lifetime maximum cumulative dose >900 mg/m2 should be avoided. Epirubicin IV is associated with a moderate or high emetic potential (depending on regimen); antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Hydration and antihyperuricemic prophylaxis may minimize potential tumor lysis syndrome.
Bladder cancer, non–muscle-invasive (off-label use): Intravesical instillation: 50 or 80 mg as a single instillation (retained for 1 hour) within 6 hours postoperatively after transurethral resection (Berrum-Svennung 2008; Oosterlinck 1993).
Breast cancer, adjuvant treatment: Usual dose: IV: 100 to 120 mg/m2 per 3- or 4-week treatment cycle as follows:
CEF-120 regimen: IV: 60 mg/m2 on days 1 and 8 every 28 days for 6 cycles in combination with cyclophosphamide and fluorouracil (Levine 2005) or
FEC-100 regimen: IV: 100 mg/m2 on day 1 every 21 days for 6 cycles in combination with cyclophosphamide and fluorouracil (Bonneterre 2005) or
Breast cancer (off-label regimens):
EC regimen: IV: 100 mg/m2 on day 1 every 21 days for 8 cycles in combination with cyclophosphamide (Piccart 2001) or
EP or EC regimen: IV: 75 mg/m2 on day 1 every 21 days for up to 6 cycles in combination with either paclitaxel or cyclophosphamide (Langley 2005) or
FEC regimen ± paclitaxel: IV: 90 mg/m2 on day 1 every 21 days for 6 cycles in combination with fluorouracil and cyclophosphamide or for 4 cycles in combination with fluorouracil and cyclophosphamide followed by paclitaxel (Martin 2008) or
FEC regimen followed by pertuzumab + trastuzumab + docetaxel: IV: 100 mg/m2 on day 1 every 21 days for 3 cycles in combination with fluorouracil and cyclophosphamide, followed by 3 cycles of pertuzumab, trastuzumab, and docetaxel (Schneeweiss 2013) or
CEF regimen: IV: 50 mg/m2 on days 1 and 8 every 21 or 28 days for 6 to 9 cycles in combination with cyclophosphamide and fluorouracil (Ackland 2001).
Soft tissue sarcoma (off-label use): IV: 25 mg/m2 on days 1, 2, and 3 every 28 days for 4 cycles (in combination with ifosfamide and mesna) (Petrioli 2002) or 60 mg/m2 on days 1 and 2 every 21 days for 5 cycles (in combination with ifosfamide, mesna, and filgrastim) (Frustaci 2001).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The manufacturer's labeling recommends considering lower doses (dose not specified) in patients with severe renal impairment (serum creatinine >5 mg/dL). Epirubicin has not been studied in patients on dialysis.
The manufacturer's labeling recommends the following adjustments (based on clinical trial information):
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times ULN: Administer 50% of recommended starting dose.
Bilirubin >3 mg/dL or AST >4 times ULN: Administer 25% of recommended starting dose.
Severe hepatic impairment (Child-Pugh class C or serum bilirubin >5 mg/dL): Use is contraindicated.
Plasma clearance of epirubicin in elderly female patients was noted to be reduced by 35%. Although no initial dosage reduction is specifically recommended, particular care should be exercised in monitoring toxicity and adjusting subsequent dosage in elderly patients (particularly females >70 years of age).
ASCO guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]).
Breast cancer (adjuvant therapy):
Hematologic toxicity: Note: Heavily treated patients, patients with preexisting bone marrow depression or neoplastic bone marrow infiltration: Lower starting doses (75 to 90 mg/m2) should be considered.
Delay day 1 dose of subsequent cycles until platelets are ≥100,000/mm3, ANC ≥1,500/mm3, and nonhematologic toxicities have recovered to ≤ grade 1.
Reduce day 1 dose in subsequent cycles to 75% of previous day 1 dose if patient experiences nadir platelet counts <50,000/mm3, ANC <250/mm3, neutropenic fever, or grade 3/4 nonhematologic toxicity during the previous cycle.
For CEF-120 regimen, reduce day 8 dose to 75% of day 1 dose if platelet counts are 75,000 to 100,000/mm3 and ANC is 1,000 to 1,499/mm3; omit day 8 dose if platelets are <75,000/mm3, ANC <1,000/mm3, or grade 3/4 nonhematologic toxicity.
Nonhematologic toxicity: Cardiac toxicity: Discontinue epirubicin if signs/symptoms of cardiomyopathy develop. Consider discontinuation if left ventricular ejection fraction decreases or if signs/symptoms of heart failure develop.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride [preservative free]:
Ellence: 50 mg/25 mL (25 mL); 200 mg/100 mL (100 mL)
Generic: 50 mg/25 mL (25 mL); 200 mg/100 mL (100 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Pharmorubicin PFS: 2 mg/mL (5 mL, 25 mL, 100 mL)
Generic: 2 mg/mL (5 mL, 25 mL, 100 mL)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 50 mg ([DSC])
Epirubicin is associated with a moderate or high emetic potential (depending on regimen); antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: Infuse over 15 to 20 minutes or slow IV push; if lower doses due to dose reduction are administered, may reduce infusion time proportionally. Do not infuse over <3 minutes. Infuse into a free-flowing IV solution (NS or D5W). Avoid the use of veins over joints or in extremities with compromised venous or lymphatic drainage.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (ESMO/EONS [Pérez Fidalgo 2012]); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Dexrazoxane: 1,000 mg/m2 (maximum dose: 2,000 mg) IV (administer in a large vein remote from site of extravasation) over 1 to 2 hours days 1 and 2, then 500 mg/m2 (maximum dose: 1,000 mg) IV over 1 to 2 hours day 3; begin within 6 hours of extravasation. Day 2 and day 3 doses should be administered at approximately the same time (± 3 hours) as the dose on day 1 (Mouridsen 2007; ESMO/EONS [Pérez Fidalgo 2012]). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (ESMO/EONS [Pérez Fidalgo 2012]).
Intravesicular administration (off-label use): Instill into bladder and retain for 1 hour (Berrum-Svennung 2008; Oosterlinck 1993).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer, adjuvant treatment: Adjuvant therapy component for primary breast cancer in patients with evidence of axillary node tumor involvement
Bladder cancer, non–muscle-invasive; Soft tissue sarcoma
EpiRUBicin may be confused with DAUNOrubicin, DOXOrubicin, eriBULin, IDArubicin, valrubicin
Ellence [US] may be confused with Elase brand name for dornase alfa [Chile, France, Malaysia]
This drug is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not always defined. Percentages reported as part of combination chemotherapy regimens.
Cardiovascular: Decreased left ventricular ejection fraction (asymptomatic; delayed: 1% to 2%), cardiac failure (≤2%), atrioventricular block, bradycardia, bundle branch block, cardiac arrhythmia, cardiomyopathy, ECG abnormality, myocarditis, non-specific T wave on ECG, sinus tachycardia, ST segment changes on ECG, tachyarrhythmia, thromboembolism, ventricular premature contractions, ventricular tachycardia
Central nervous system: Lethargy (1% to 46%)
Dermatologic: Alopecia (70% to 96%), skin rash (1% to 9%), skin changes (1% to 5%)
Endocrine & metabolic: Amenorrhea (69% to 72%), hot flash (5% to 39%)
Gastrointestinal: Nausea and vomiting (83% to 92%; grades 3/4: 22% to 25%), mucositis (9% to 59%; grades 3/4: ≤9%), diarrhea (7% to 25%), anorexia (2% to 3%), abdominal pain, esophagitis, neutropenic enterocolitis, stomatitis, toxic megacolon
Genitourinary: Menopause (premature or early)
Hematologic & oncologic: Neutropenia (54% to 80%; grades 3/4: 11% to 67%; nadir: 10 to 14 days; recovery: by day 21), leukopenia (50% to 80%; grades 3/4: 2% to 59%), anemia (13% to 72%; grades 3/4: ≤6%), thrombocytopenia (5% to 49%; grades 3/4: ≤5%), febrile neutropenia (grades 3/4: ≤6%), acute lymphocytic leukemia, acute myelocytic leukemia, myelodysplastic syndrome
Hepatic: Ascites, hepatomegaly, increased serum transaminases
Hypersensitivity: Hypersensitivity reaction
Infection: Infection (15% to 22%; grades 3/4: ≤2%)
Local: Injection site reaction (3% to 20%; grades 3/4: <1%)
Ophthalmic: Conjunctivitis (1% to 15%)
Respiratory: Dyspnea, pulmonary edema
Miscellaneous: Fever (1% to 5%)
<1%, postmarketing, case reports: Anaphylaxis, arterial embolism, burning sensation of gastrointestinal tract, chills, dehydration, erythema, flushing, gastrointestinal erosion, gastrointestinal hemorrhage, gastrointestinal pain, gastrointestinal ulcer, hyperuricemia, nail hyperpigmentation, oral mucosa hyperpigmentation, phlebitis, pneumonia, pulmonary embolism, radiation recall phenomenon, red urine discoloration, sepsis, shock, skin hyperpigmentation, skin photosensitivity, thrombophlebitis, urticaria
Severe hypersensitivity to epirubicin, other anthracyclines, anthracenediones, or any component of the formulation; severe myocardial insufficiency, recent myocardial infarction, or severe arrhythmias; previous treatment with anthracyclines up to the maximum cumulative dose; severe persistent drug-induced myelosuppression; severe hepatic impairment (Child-Pugh class C or serum bilirubin >5 mg/dL)
Canadian labeling: Additional contraindications (not in the US labeling): Marked persistent myelosuppression induced by prior treatment with other chemotherapy agents or by radiotherapy
Concerns related to adverse effects:
• Bone marrow suppression: Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur. Leukopenia, neutropenia, thrombocytopenia, and anemia may occur.
• Cardiac toxicity Myocardial damage, including acute left ventricular failure, can occur with epirubicin. The risk of cardiomyopathy is proportional to the cumulative exposure, with incidence rates from 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 cardiomyopathy is further increased with concomitant cardiotoxic therapy. Early toxicity may consist of sinus tachycardia and/or ECG changes, such as nonspecific ST-T wave changes. Tachycardia, including premature ventricular contractions and ventricular tachycardia, as well as bradycardia, have occurred. Atrioventricular and bundle-branch block have also been reported. These early cardiotoxicities are not necessarily predictive of subsequent delayed cardiotoxicity and are not necessarily a reason to suspend epirubicin therapy. Delayed cardiotoxicity is typically caused by cardiomyopathy, which presents as decreased left ventricular ejection fraction (LVEF) and/or signs/symptoms of heart failure. Delayed cardiotoxicity typically develops late during epirubicin therapy, or within 2 to 3 months after completion of epirubicin; cardiotoxicity has been reported several months to years after therapy termination. The recommended lifetime epirubicin cumulative dose is 900 mg/m2; avoid cumulative doses above this. Total cumulative dose should take into account prior treatment with other anthracyclines or anthracenediones, previous or concomitant treatment with other cardiotoxic agents, or irradiation of chest. Although the risk increases with cumulative dose, irreversible cardiotoxicity may occur at any dose level. Active or dormant cardiovascular disease, concurrent or recent administration of cardiotoxic drugs, prior therapy with other anthracyclines or anthracenediones, or prior or concurrent chest (mediastinal/pericardial area) irradiation may increase the risk of developing late cardiac toxicity. Children may be at increased risk for developing acute and/or delayed cardiotoxicity. The half-life of other cardiotoxic agents (eg, trastuzumab) must be considered in sequential therapy.
ASCO has developed guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]). According to the guidelines, the risk of cardiac dysfunction is increased with the following:
- High-dose anthracycline therapy (eg, doxorubicin ≥250 mg/m2, epirubicin ≥600 mg/m2)
- High-dose radiotherapy (≥30 Gy) with the heart in the treatment field
- Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) in combination with lower-dose radiotherapy (<30 Gy) with the heart in the treatment field
- Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) or trastuzumab alone AND any of the following risk factors: multiple cardiovascular risk factors (≥2 risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity (during or after completion of therapy), or older age (≥60 years) at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment
- Treatment with lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) followed by trastuzumab (sequential therapy)
- Other risk factors for anthracycline-induced cardiotoxicity include age 60 and older at time of treatment and 2 or more cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment.
The ASCO guidelines recommend a comprehensive assessment in patients with cancer that includes a history and physical examination and screening for cardiovascular disease risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and smoking. An echocardiogram should be obtained prior to initiating potentially cardiotoxic therapies. Modifiable risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) should be actively managed before initiating potentially cardiotoxic therapies. Consider cardioprotectants (eg, dexrazoxane) or continuous infusions in patients who are likely to receive high-dose anthracycline therapy. In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or multigated acquisition (MUGA) scan may be utilized. Serum cardiac biomarkers are recommended, along with referral to a cardiologist if indicated.
• Extravasation: Extravasation of epirubicin may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. If extravasation occurs, immediately terminate administration and apply ice to the affected area. Local tissue injury may manifest as blistering, ulceration, or necrosis. Consider extravasation if burning/stinging occurs during infusion, or if other signs indicating perivenous infiltration or extravasation are present; extravasation may occur even when blood return is present on aspiration, or in patients without burning/stinging symptoms. Injection into a small vein or repeated administration in the same vein may result in venous sclerosis. Avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If perivenous infiltration occurs, immediately discontinue infusion and restart in another vein. If appropriate, dexrazoxane may be considered (if within 6 hours of extravasation).
• Secondary malignancy: Secondary acute myelogenous leukemia and myelodysplastic syndrome occur at a higher incidence in patients treated with anthracyclines, including epirubicin. The latency period for secondary leukemias may be short (1 to 3 years).
• Thromboembolic events: Thrombophlebitis and thromboembolic phenomena (including pulmonary embolism) have occurred; some cases have been fatal. Local phlebitis or thrombophlebitis may be preceded by facial flushing and erythematous streaking along the vein (may be indicative of excessively rapid administration).
• Tumor lysis syndrome: Epirubicin may cause tumor lysis syndrome (TLS), particularly in patients with rapid tumor proliferation.
Special populations:
• Older age: Females ≥70 years of age should be closely monitored for toxicity due to the possibility of decreased epirubicin clearance.
• Pediatric: Children may be at increased risk for developing acute and delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended.
• Radiation recipients: Epirubicin may increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including cutaneous and pulmonary toxicity, may occur in patients who receive epirubicin after prior radiation therapy.
Other warnings/precautions:
• Immunizations: Patients should not be immunized with live or live-attenuated viral vaccines during or shortly after treatment; serious or fatal infection may result in immunocompromised patients. Inactivated vaccines may be administered; however, response may be diminished.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bevacizumab: May enhance the cardiotoxic effect of Anthracyclines. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of EpiRUBicin. Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Cyclophosphamide: May enhance the cardiotoxic effect of Anthracyclines. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fam-Trastuzumab Deruxtecan: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Margetuximab: Anthracyclines may enhance the adverse/toxic effect of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taxane Derivatives: May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Trastuzumab: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who could become pregnant should be advised to use effective contraception and avoid becoming pregnant during treatment. Patients with partners who could become pregnant should use effective contraception during and after treatment. Epirubicin may cause irreversible amenorrhea.
Adverse events were observed in animal reproduction studies. Pregnant caregivers should avoid handling epirubicin.
Limited information is available from a retrospective study of patients who received epirubicin (in combination with cyclophosphamide or weekly as a single-agent) during the second or third (prior to week 35) trimester for the treatment of pregnancy-associated breast cancer (Ring 2005) and from a study of women who received epirubicin (weekly as a single-agent) at gestational weeks 16 through 30 for the treatment of pregnancy-associated breast cancer (Peccatori 2009). Some pharmacokinetic properties of epirubicin may be altered in pregnant women (van Hasselt 2014). The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy (ESMO [Peccatori 2013]); the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). If chemotherapy is indicated, it should not be administered in the first trimester, but may begin in the second trimester. There should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation.
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).
It is not known if epirubicin is present in human breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for ≥7 days after the last epirubicin dose.
Baseline and repeated measurements of CBC with differential, LFTs (total bilirubin, ALT, AST), serum creatinine. If at risk for tumor lysis syndrome, monitor serum uric acid, potassium, calcium, phosphate, and serum creatinine after initial dose. Assess left ventricular ejection fraction (LVEF) before and regularly during and after epirubicin treatment. The method used for assessment of LVEF (ECG or MUGA) should be consistent during routine monitoring. Obtain ECG. Evaluate pregnancy status prior to treatment initiation (in patients who could become pregnant). Monitor injection site during infusion for possible extravasation or local reactions. Monitor for signs/symptoms of tumor lysis syndrome. Monitor for secondary malignancy.
Cardiovascular monitoring (ASCO [Armenian 2017]): Comprehensive assessment prior to treatment, including a history and physical examination and screening for cardiovascular disease risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and smoking; echocardiogram (prior to treatment). In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or multigated acquisition (MUGA) scan may be utilized; obtain serum cardiac biomarkers.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Epirubicin is an anthracycline antineoplastic agent; known to inhibit DNA and RNA synthesis by steric obstruction after intercalating between DNA base pairs; active throughout entire cell cycle. Intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Also inhibits DNA helicase, and generates cytotoxic free radicals.
Distribution: Vdss: 21 to 27 L/kg
Protein binding: ~77% to albumin
Metabolism: Extensively via hepatic and extrahepatic (including RBCs) routes
Half-life elimination: Triphasic; Mean terminal: 33 hours
Excretion: Feces (34% to 35%); urine (20% to 27%)
Renal function impairment: Clearance was reduced by 50% in patients with serum creatinine ≥5 mg/dL.
Hepatic function impairment: Clearance was reduced by ~30% in patients with elevated AST levels and normal bilirubin, and by ~50% in patients with elevated AST and bilirubin levels, as compared to patients with normal hepatic function.
Geriatric: Plasma clearance of epirubicin in elderly female patients was reduced by 35% as compared to younger female patients.
Solution (Ellence Intravenous)
50 mg/25 mL (per mL): $2.24
200 mg/100 mL (per mL): $2.73
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