epirubicin (Rx)

>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)

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

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.

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%)

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