Dosing and uses of Epirubicin (Ellence, Pharmorubicin)
Adult dosage forms and 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
Pediatric dosage forms and strengths
Safety & efficacy not established
Epirubicin (Ellence, Pharmorubicin) adverse (side) 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
Severe myelosuppression 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)
Cardiotoxicity
- Myocardial toxicity, 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
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
Hypersensitivity
Baseline ANC<1500/mm³
Cardiomyopathy and/or heart failure, recent MI, or severe arrhythmias
Cumulative dose achieved in previous anthracycline treatment
Severe hepatic impairment
Cautions
Vesicant
Increased dose-related risk of seondary leukemia (AML, MDS)
Risk of cardiomyopathy
Emetogenic
Thrombophlebitis may occur
Women of child-bearing potential should be advised to avoid becoming pregnant during treatment and should use effective contraceptive methods
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk; do not nurse
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 of Epirubicin (Ellence, Pharmorubicin)
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
