Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 2mg/mL
powder for reconstitution
- 50 mg
- 200 mg
Adjuvant Breast Cancer Treatment
Option 1 (Day 1 dose schedule)
- Day 1: Epirubicin 100 mg/m² IV, AND 5-fluorouracil 500 mg/m² IV, AND cyclophosphamide 500 mg/m² IV
- Repeat q21Days x 6 cycles
Option 2 (Divided dose schedule)
- First dose divided equally between days 1 & 8: Epirubicin 60 mg/m² IV, AND 5-fluorouracil 500 mg/m² IV, AND
- Days 1-14: Cyclophosphamide 75 mg/m² PO
- Repeat q28Days x 6 cycles
Dose Modifications
Adjustment if Total Dose Given on Day 1
- Administer 75% of Day 1 dose in subsequent cycles if nadir platelet count <50,000/mm³, absolute neutrophil count (ANC) < 250/mm³, neutropenic fever present, grade 3/4 nonhematologic toxicity observed
Divided Dose Adjustment
- Administer 75% of Day 1 dose on Day 8 if platelet count 75,000-100,000/mm³ and ANC < 1000-1499/mm³
- Do not administer dose on day 8 if platelet count < 75,000/mm³ and ANC < 1000/mm³
Bone Marrow Dysfunction
- Consider lower starting dose (75-90 mg/m²)
Renal Impairment
SCr >5 mg/dL [>442 micromoles/L]: Decrease dose by 50%; test cardiac ejection fraction via MUGA before starting treatment
Hepatic Impairment
Billirubin < 1.2 mg/dL: Dose adjustment not necessary
Bilirubin 1.2-3 mg/dL or AST 2-4 x ULN: 50% of recommended starting dose
Bilirubin >3 mg/dL or AST > 4 x ULN: 25% of recommended starting dose (ie, decrease starting dose by 75%)
Severe hepatic impairment: Not recommended
Monitoring
LFTs, CBC, creatinine; multi-gated radionuclide angiography or ECHO
Soft Tissue Sarcoma (Orphan)
epirubicin-conjugated polymer micelles
Orphan designation for treatment of soft tissue sarcoma
Sponsor
- NanoCarrier Co., Ltd; Chuou 144-15, 226-39 Wakashiba; Kashiwa; Japan
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Alopecia (96%)
Nausea and vomiting (92%)
Leukopenia or neutropenia (80%)
Amenorrhea (72%)
Anemia (72%)
Mucositis (59%)
Thrombocytopenia (49%)
Lethargy (46%)
Hot flashes (39%)
Diarrhea (25%)
Conjunctivitis (15%)
1-10%
Rash (9%)
Fever (5%)
Skin changes (5%)
Anorexia (3%)
<1%
Acute lymphoid leukemia
Acute myelogenous leukemia
Atrioventricular block
Esophagitis
Hyperpigmentation
Myelodysplastic syndrome
Frequency Not Defined
Myocardial toxicity (including CHF)
Severe myelosuppression
Risk of secondary AML
Postmarketing Reports
Infections and infestations: Sepsis, pneumonia
Immune system disorders: Anaphylaxis
Metabolism and nutrition disorders: Dehydration, hyperuricemia
Vascular disorders: Shock, hemorrhage, embolism arterial, thrombophlebitis, phlebitis
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 1-2 days after administration
General disorders and administration site conditions: Fever, chills
Injury, poisoning and procedural complications: Chemical cystitis (following intravesical administration)
Warnings
Black Box Warnings
Reduce dosage with impaired hepatic function
Myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur
Administer only under the supervision of physician experienced in the use of cancer chemotherapeutic agents
Extravasation
- Severe local tissue necrosis associated with extravasation during administration; administer only by IV route (not IM or SC); immediately terminate the drug and apply ice to the affected area
Cardiotoxicity
- Myocardial damage, including acute left ventricular failure can occur; manifested in its most severe form by potentially fatal congestive heart failure (CHF); may occur months to years after treatment discontinued
- Probability of cardiotoxicity estimated to be 0.9% at a cumulative dose of 550 mg/m², 1.6% at 700 mg/m², and 3.3% at 900 mg/m²
- Risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy; assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment
Secondary malignancies
- Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS)
- More common when given in combination with DNA-damaging antineoplastic agents, patients heavily pretreated with cytotoxic drugs, or with escalated anthracycline doses
- Cumulative risk of developing treatment-related AML or MDS estimated as 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years
Contraindications
Severe hypersensitivity to drug, other anthracyclines, or anthracenediones
Baseline ANC<1500/mm³
Cardiomyopathy and/or heart failure, recent MI, or severe arrhythmias
Severe myocardial insufficiency
Cumulative dose achieved in previous anthracycline treatment
Severe persistent drug-induced myelosuppression
Severe hepatic impairment (Child-Pugh Class C or serum bilirubin level greater than 5 mg/dL)
Cautions
Lysis syndrome may occur; evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment; consider hydration, urine alkalinization, and prophylaxis with allopurinol to minimize potential complications of hyperuricemia and tumor lysis syndrome
Thrombophlebitis and thromboembolic events, including pulmonary embolism (in some cases fatal) reported with therapy; venous sclerosis may result from an injection into small vessel or from repeated injections into same vein
Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents may result in serious or fatal infections
Administration after previous radiation therapy may induce an inflammatory recall reaction at site of irradiation
Therapy can cause fetal harm; advise patients of potential risk to a fetus and to use effective contraception
Women of child-bearing potential should be advised to avoid becoming pregnant during treatment and should use effective contraceptive methods
Pregnancy & Lactation
Pregnancy
Verify pregnancy status in female patients of reproductive potential prior to initiating
Based on findings from animal studies and mechanism of action, drug can cause fetal harm when administered to a pregnant woman; avoid use during the 1st trimester
Available human data do not establish presence or absence of major birth defects and miscarriage related to use during the 2nd and 3rd trimesters; there are reports of fetal and/or neonatal cardiotoxicity following in utero exposure to epirubicin
There have been rare reports of fetal and/or neonatal transient ventricular hypokinesia, transient elevation of cardiac enzymes, and a case of fetal demise from suspected anthracycline-induced cardiotoxicity following in utero exposure to epirubicin in 2nd and/or 3rd trimesters
Cardiotoxicity is a known risk of anthracycline treatment in adults; monitor fetus and/or neonate for cardiotoxicity and perform testing consistent with community standards of care
Advise pregnant women and females of reproductive potential of potential risk to a fetus
Animal data
- In animal reproduction studies in pregnant rats, drug was embryo-fetal lethal and caused structural abnormalities when administered during organogenesis at doses less than maximum recommended human dose on a body surface area basis
Contraception
- Can cause fetal harm in females when administered to a pregnant woman; advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after last dose
- Based on its mechanism of action and genotoxicity studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after last dose
- Advise male patients with pregnant partners to use condoms during treatment and for at least 7 days after last dose
Infertility
- Based on clinical findings and animal studies, therapy may impair female fertility and result in amenorrhea; premature menopause can occur; recovery of menses and ovulation is related to age at treatment
- Based on clinical findings and animal studies in males, therapy may cause oligospermia, azoospermia, and permanent loss of fertility; sperm counts have been reported to return to normal levels in some men; may occur several years after end of therapy
Lactation
There are no data on presence of drug in human milk, effects on breastfed child, or on milk production; drug is present in rat milk; when a drug is present in animal milk it is likely the drug will be present in human milk
Because of potential for serious adverse reactions in breastfed child, advise lactating women not to breastfeed during treatment and for at least 7 days after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Anthracycline; intercalates between DNA base pairs and triggers cleavage by topoisomerase II, which results in cytocidal activity
Inhibits DNA helicase and generates cytotoxic free radicals
Pharmacokinetics
Half-Life: 31-35 hr
Protein Bound: 77%
Vd: 21-27 L/kg
Metabolism: Hepatic
Clearance: 65-69 L/hr
Excretion: Feces (34-35%) & urine (20-27%)
Administration
IV Incompatibilities
Additive: Alkaline solutions, heparin, fluorouracil
Syringe: Fluorouracil, ifosfamide with mesna
IV Compatibilities
Additive, Syringe: ifosfamide
IV Administration
Administer infuse into tubing of a freely flowing infusion (NS or D5W) over 3-5 min
Avoid extravasation, associated with severe ulceration & soft tissue necrosis; flush with 5-10 mL of IV solution before & after drug administration
Extravasation Management
See Totect
Storage
Store refrigerated
Protect from light
Solution should be used within 24 hr of penetrating rubber stopper
Images
Patient Handout
Formulary
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