epirubicin (Rx)

Brand and Other Names:Ellence, Pharmorubicin
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Dosing & Uses

AdultPediatric

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

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Interactions

Interaction Checker

and epirubicin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            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)

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            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

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            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.

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            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%)

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            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

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.