(ep i ROO bi sin)
- Epirubicin HCl
- Epirubicin Hydrochloride
- Pidorubicin Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 50 mg (1 ea [DSC])
Brand Names: U.S.
- Antineoplastic Agent, Anthracycline
- Antineoplastic Agent, Topoisomerase II Inhibitor
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.
Vdss: 21 to 27 L/kg
Extensive via hepatic and extrahepatic (including RBCs) routes
Feces (34% to 35%); urine (20% to 27%)
Triphasic; Mean terminal: 33 hours
~77% to albumin
Special Populations: Renal Function Impairment
Clearance was reduced by 50% in patients with serum creatinine ≥5 mg/dL.
Special Populations: 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.
Special Populations: Elderly
Plasma clearance of epirubicin in elderly female patients was reduced by 35% as compared to younger female patients.
Use: Labeled Indications
Breast cancer, adjuvant treatment: Adjuvant therapy component for primary breast cancer in patients with evidence of axillary node involvement following tumor resection
Off Label Uses
Data from a large, randomized, phase III trial supports the use of epirubicin in combination with cisplatin and fluorouracil (ECF regimen) pre- and postoperatively for the management of adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus [Cunningham 2006]. Another large phase III trial (REAL-2) investigated whether fluorouracil could be replaced by capecitabine, and cisplatin could be replaced by oxaliplatin, in the ECF regimen for the treatment of esophagogastric cancers. Data from the two-by-two design showed that capecitabine and oxaliplatin were as effective as fluorouracil and cisplatin, respectively (in combination with epirubicin) [Cunningham 2008].
Data from two large, randomized, phase III trials supports the use of epirubicin in combination with cisplatin and fluorouracil (ECF regimen) for the management of adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus [Cunningham 2006], [Waters 1999]. Another large phase III trial (REAL-2) investigated whether fluorouracil could be replaced by capecitabine, and cisplatin could be replaced by oxaliplatin, in the ECF regimen for the treatment of esophagogastric cancers. Data from the two-by-two design showed that capecitabine and oxaliplatin were as effective as fluorouracil and cisplatin, respectively (in combination with epirubicin) [Cunningham 2008].
Data from a small phase II trial in patients with nonmetastatic or extremity osteosarcoma supports the use of epirubicin (in combination with cisplatin, ifosfamide and mesna) for 3 cycles before and 3 cycles after surgery [Basaran 2007]. Additional trials may be necessary to further define the role of epirubicin in this condition.
Soft tissue sarcoma
Data from a phase II trial as well as from a phase III randomized trial support the use of epirubicin in combination with ifosfamide/mesna for the adjuvant treatment of soft tissue sarcoma after surgical resection [Frustaci 2001], [Petrioli 2002]. Additional trials may be necessary to further define the role of epirubicin in this condition.
Hypersensitivity to epirubicin, other anthracyclines, anthracenediones, or any component of the formulation; cardiomyopathy and/or heart failure, recent myocardial infarction, severe arrhythmias; previous treatment with anthracyclines up to the maximum cumulative dose
Canadian labeling: Additional contraindications (not in the US labeling): Marked persistent myelosuppression induced by prior treatment with other chemotherapy agents or by radiotherapy; severe hepatic impairment.
Note: Patients receiving 120 mg/m2/cycle as part of combination therapy (CEF-120 regimen) should also receive prophylactic antibiotic therapy with sulfamethoxazole/trimethoprim or a fluoroquinolone. Lower 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. The recommended lifetime maximum dose is 900 mg/m2. Epirubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2016).
Breast cancer, adjuvant treatment: IV: Usual dose: 100 to 120 mg/m2 per 3- or 4-week treatment cycle as follows:
60 mg/m2 on days 1 and 8 every 28 days for 6 cycles in combination with cyclophosphamide and fluorouracil (CEF-120 regimen; Levine 2005) or
100 mg/m2 on day 1 every 21 days for 6 cycles in combination with cyclophosphamide and fluorouracil (FEC-100 regimen; Bonneterre 2005) or
Breast cancer (off-label regimens): IV:
EC regimen: 100 mg/m2 on day 1 every 21 days for 8 cycles in combination with cyclophosphamide (Piccart 2001) or
EP or EC regimen: 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: 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: 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: 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)
Esophageal cancer (off-label use): IV:
ECF, ECX, EOF, and EOX regimens: 50 mg/m2 on day 1 every 21 days for up to 8 cycles in combination with cisplatin (C), oxaliplatin (O), fluorouracil (F), and/or capecitabine (X) (Cunningham 2008) or
ECF regimen: 50 mg/m2 on day 1 every 21 days for 3 preoperative and 3 postoperative cycles in combination with cisplatin and fluorouracil (Cunningham 2006)
Gastric cancer (off-label use): IV:
ECF, ECX, EOF, and EOX regimens: 50 mg/m2 on day 1 every 21 days for up to 8 cycles in combination with cisplatin (C), oxaliplatin (O), fluorouracil (F), and/or capecitabine (X) (Cunningham 2008; Waters 1999) or
ECF regimen: 50 mg/m2 on day 1 every 21 days for 3 preoperative and 3 postoperative cycles in combination with cisplatin and fluorouracil (Cunningham 2006)
Osteosarcoma (off-label use): IV: 90 mg/m2 on day 1 every 21 days for 3 cycles before surgery and 90 mg/m2 on day 1 every 28 days for 3 cycles after surgery (in combination with cisplatin, ifosfamide and mesna) (Basaran 2007)
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 toxicity (breast cancer; labeled dosing):
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 ≥1500/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 1000 to 1499/mm3; omit day 8 dose if platelets are <75,000/mm3, ANC <1000/mm3, or grade 3/4 nonhematologic toxicity
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).
Dosing: Renal Impairment
The manufacturer's labeling recommends lower doses (dose not specified) in patients with severe renal impairment (serum creatinine >5 mg/dL). Other sources (Aronoff 2007) suggest no dosage adjustment is needed for CrCl <50 mL/minute.
Dosing: Hepatic Impairment
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 the upper limit of normal: Administer 50% of recommended starting dose
Bilirubin >3 mg/dL or AST >4 times the upper limit of normal: Administer 25% of recommended starting dose
Severe hepatic impairment: Use is not recommended (has not been studied).
ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: 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 nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).
Reconstitute lyophilized powder with sterile water for injection (25 mL for the 50 mg vial) to a final concentration of 2 mg/mL. Shake vigorously; may take several minutes for dissolution. May be further diluted with sterile water for injection.
Epirubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; 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 (Perez 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: Adults: 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; Perez Fidalgo 2012). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Children and Adults: 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 (Perez Fidalgo 2012).
Protect from light.
Solution: Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Product may “gel” at refrigerated temperatures; will return to slightly viscous solution after 2 to 4 hours at room temperature (15°C to 25°C). Discard unused solution from single dose vials within 24 hours of entry.
Lyophilized powder: Store at room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Reconstituted solutions are stable for 24 hours when stored at 2°C to 8°C (36°F to 46°F) or at room temperature.
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline, Systemic). 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. Consider therapy modification
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bevacizumab: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline, Systemic). Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Antineoplastic Agents (Anthracycline, Systemic). Antineoplastic Agents (Anthracycline, Systemic) 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. Monitor therapy
Cimetidine: May increase the serum concentration of EpiRUBicin. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Cyclophosphamide: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline, Systemic). Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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. Consider therapy modification
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Taxane Derivatives: May enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Consider therapy modification
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Trastuzumab: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline, Systemic). 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. Consider therapy modification
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
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% (Limited to important or life-threatening): Anaphylaxis, arterial embolism, burning sensation of gastrointestinal tract, chills, dehydration, erythema, 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
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: May cause severe myelosuppression, including leukopenia, thrombocytopenia, and anemia. Myelosuppression is the dose-limiting toxicity. Obtain baseline and periodic blood counts. Patients should recover from myelosuppression due to prior chemotherapy treatment before beginning treatments. Severe neutropenia and severe infections may require supportive care.
• Extravasation: [US Boxed Warning]: For IV administration only. Vesicant; if extravasation occurs, severe local tissue damage and necrosis may occur. Not for IM or SubQ use. Injection into a small vein or repeated administration in the same vein may result in venous sclerosis. 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.
• Gastrointestinal toxicity: Epirubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2016).
• Myocardial toxicity: Myocardial toxicity, including fatal heart failure (HF) may occur, particularly in patients who have received prior anthracyclines (or anthracenediones), prior or concomitant radiotherapy to the mediastinal/pericardial area, who have preexisting cardiac disease (active or dormant), or with concomitant cardiotoxic medications. Cardiotoxicity may be concurrent or delayed (months to years after treatment). The risk of HF is ~0.9% at a cumulative dose of 550 mg/m2, ~1.6% at a cumulative dose of 700 mg/m2, and ~3.3% at a cumulative dose of 900 mg/m2. Cardiotoxicity may also occur at lower cumulative doses or without risk factors. The risk of delayed cardiotoxicity increases more steeply with cumulative doses >900 mg/m2, and this dose should be exceeded only with extreme caution. The maximum cumulative dose used in adjuvant studies was 720 mg/m2. Cardiotoxicity is dose-limiting. Early toxicity may consist of tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia. Electrocardiographic changes including ST-T wave changes, atrioventricular and bundle-branch block have also been reported. These effects are not necessarily predictive of subsequent delayed cardiotoxicity. Delayed toxicity is typically caused by cardiomyopathy which presents as decreased left ventricular ejection fraction (LVEF) and/or signs/symptoms of HF (eg, tachycardia, dyspnea, pulmonary edema, edema, hepatomegaly, ascites, pleural effusion, gallop rhythm). 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. Patients with active or dormant cardiovascular disease, concurrent administration of cardiotoxic drugs, prior therapy with other anthracyclines or anthracenediones, prior or concurrent chest irradiation, advanced age, and infants and children are at increased risk. Children are at increased risk for developing delayed cardiotoxicity. Regular monitoring of LVEF and discontinuation at the first sign of impairment is recommended especially in patients with cardiac risk factors or impaired cardiac function. Discontinue treatment with signs of decreased LVEF. The half-life of other cardiotoxic agents (eg, trastuzumab) must be considered in sequential therapy.
• Secondary malignancy: [US Boxed Warning]: Treatment with anthracyclines (including epirubicin) may increase the risk of secondary acute myeloid leukemia (AML). AML is more common when given in combination with other antineoplastic agents, in patients who have received multiple courses of previous chemotherapy, or with escalated anthracycline doses. In breast cancer patients, the risk for treatment-related AML or myelodysplastic syndrome (MDS) was estimated at 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years after treatment. The latency period for secondary leukemias may be short (1 to 3 years).
• Thromboembolic events: Thrombophlebitis and thromboembolic phenomena (including pulmonary embolism) have occurred.
• Tumor lysis syndrome: May cause tumor lysis syndrome (TLS). Although TLS does not generally occur in patients with breast cancer, if TLS risk is suspected, consider monitoring serum uric acid, potassium, calcium, phosphate and serum creatinine after initial administration; hydration and antihyperuricemic prophylaxis may minimize potential TLS complications.
• Hepatic impairment: [US Boxed Warning]: Dosage reduction is recommended in patients with mild-to-moderate hepatic impairment; use is not recommended in severe hepatic impairment. Evaluate hepatic function at baseline and during treatment. Epirubicin is predominantly hepatically eliminated; impaired hepatic function may lead to increased exposure and toxicity.
• Renal impairment: Dosage reduction is recommended in patients with serum creatinine >5 mg/dL. Evaluate renal function at baseline and during treatment. Has not been studied in patients on dialysis.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Elderly: Women ≥70 years of age should be closely monitored for toxicity.
• 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 have radiosensitizing activity; radiation recall (inflammatory) has also been reported.
• Appropriate use: Patients should recover from acute toxicities (stomatitis, myelosuppression, infections) prior to initiating treatment. Assess baseline labs (blood counts, bilirubin, ALT, AST, serum creatinine) and cardiac function (with LVEF). Prophylactic antibiotics should be administered with the CDF-120 regimen.
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Immunizations: Patients should not be immunized with live viral vaccines during or shortly after treatment. Inactivated vaccines may be administered (response may be diminished).
Baseline and repeated measurements of CBC with differential, liver function tests, serum creatinine, electrolytes, ECG, and LVEF. The method used for assessment of LVEF (echocardiogram or MUGA) should be consistent during routine monitoring. Monitor injection site during infusion for possible extravasation or local reactions.
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. Women of childbearing potential should be advised to use effective contraception and avoid becoming pregnant during treatment. Men undergoing treatment should use effective contraception. Epirubicin may cause irreversible amenorrhea in premenopausal women.
Limited information is available from a retrospective study of women 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 (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).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience urine discoloration, hot flashes, lack of appetite, mouth irritation, mouth sores, hair loss, amenorrhea, or eye irritation. Have patient report immediately to prescriber signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood), signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish), signs of infection, severe dizziness, passing out, severe nausea, vomiting, severe diarrhea, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding) severe loss of strength and energy, or severe injection site redness, burning, pain, edema, or irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: antibiotics/antineoplastics
Other brands: Ellence