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epiRUBicin (Monograph)

Brand name: Ellence
Drug class: Antineoplastic Agents
VA class: AN200
Chemical name: (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-α-l-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1- methoxy-5,12-naphthacenedione hydrochloride
Molecular formula: C27H29NO11•HCl
CAS number: 56390-09-1

Medically reviewed by on Jun 28, 2023. Written by ASHP.


  • Severe local tissue necrosis if extravasation occurs. Do not administer IM or sub-Q.

  • Possible cardiotoxicity and potentially fatal CHF during or after therapy. Increased risk of CHF with cumulative doses >900 mg/m2; exceed this cumulative dose with extreme caution. Toxicity may occur at lower cumulative doses, regardless of whether cardiac risk factors are present. Cardiac effects of epirubicin and other anthracyclines or anthracenediones may be additive.

  • Possible secondary acute myelogenous leukemia (AML); risk of refractory AML increases when epirubicin is combined with other DNA-damaging antineoplastics, after extensive exposure to cytotoxic drugs, or when anthracycline doses have been escalated.

  • Reduce dosage in patients with hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

  • Severe myelosuppression may occur.

  • Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.


Anthracycline glycoside antineoplastic antibiotic; the 4′-epimer of doxorubicin; a semisynthetic derivative of daunorubicin.

Uses for epiRUBicin

Breast Cancer

A component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast carcinoma; efficacy was established in combination with cyclophosphamide and fluorouracil.

epiRUBicin Dosage and Administration



Extremely irritating to tissues. Administer IV only; do not administer IM or sub-Q.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer slowly into tubing of a freely running IV infusion of 0.9% sodium chloride or 5% dextrose injection. Do not use veins over joints or in extremities with compromised venous or lymphatic drainage.

Avoid extravasation. If signs or symptoms of extravasation occur, immediately stop the injection or infusion and restart at another site.

Handle cautiously (by trained nonpregnant personnel); use protective equipment (e.g., latex gloves) and wash hands after removal of the latex gloves.

Immediately treat accidental contact with the skin, mucous membranes, or eyes by copious lavage with water, soap and water, or sodium bicarbonate solution, but avoid abrasion of skin by use of a scrub brush; seek prompt medical attention.

Rate of Administration

Usually administered over 3–20 minutes, depending on the volume of the infusion solution and the dosage.

Rapid administration may cause local erythematous streaking along the vein and/or facial flushing; local phlebitis or thrombophlebitis may follow.


Available as epirubicin hydrochloride; dosage expressed in terms of the salt.


Breast Cancer

100–120 mg/m2 in repeated 3- to 4-week cycles; give total dose for each cycle as a single dose on day 1 or as 2 equally divided doses on days 1 and 8.

In clinical trials, the 100-mg/m2 epirubicin hydrochloride regimen included fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2, with all drugs administered IV on day 1 of a 21-day cycle and repeated for 6 cycles.

In clinical trials, the 120-mg/m2 epirubicin hydrochloride regimen was given IV as 60 mg/m2 of the anthracycline and fluorouracil 500 mg/m2 on days 1 and 8 of each cycle combined with oral cyclophosphamide 75 mg/m2 on days 1–14 of each cycle, with the cycles being repeated at 28-day intervals, for 6 cycles.

Adjust dosage after first treatment cycle based on hematologic and nonhematologic toxicities.

In patients with nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANCs) <250/mm3, neutropenic fevers, or grade 3 or 4 nonhematologic toxicity, reduce day-1 dose of each antineoplastic agent in subsequent cycles to 75% of the day-1 dose given in current cycle.

Delay day-1 chemotherapy in subsequent cycles until platelet counts are ≥100,000/mm3, ANCs are ≥1500/mm3, and nonhematologic toxicities have recovered to grade 1 or better.

If epirubicin hydrochloride dose is divided between days 1 and 8, reduce the day-8 dose of each drug to 75% of the day-1 dose if platelet counts and ANCs are 75,000–100,000 and 1000–1499/mm3, respectively.

If day-8 platelet counts or ANCs are <75,000 or 1000/mm3, respectively, or grade 3 or 4 nonhematologic toxicity has occurred, omit day-8 dose of each drug.

Special Populations

Hepatic Impairment

In clinical studies, patients with serum bilirubin concentration of 1.2–3 mg/dL or AST concentration 2–4 times the upper limit of normal (ULN) received 50% of recommended initial dosage of epirubicin hydrochloride.

In clinical studies, patients with serum bilirubin concentration of >3 mg/dL or AST >4 times the ULN received 25% of initial recommended dosage of epirubicin hydrochloride.

Epirubicin is not recommended in patients with severe hepatic impairment.

Renal Impairment

Consider dosage reduction if Scr is >5 mg/dL; not studied in those undergoing dialysis.

Bone Marrow Impairment

Consider decreasing dosage for the initial cycle to 75–90 mg/m2 in patients with bone marrow impairment (e.g., extensive pretreatment, preexisting myelosuppression, neoplastic bone marrow infiltration).

Cautions for epiRUBicin




Adequate Patient Evaluation and Monitoring

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.

Patients must have recovered from acute toxicities (e.g., stomatitis, neutropenia, thrombocytopenia, generalized infections) of prior cytotoxic therapy before starting treatment with epirubicin.

Prior to and during therapy, assess hematopoietic, hepatic, renal, and cardiac function; monitor for clinical complications associated with myelosuppression (e.g., granulocytopenia, infections) and potential cardiotoxicity (e.g., CHF), especially with increasing cumulative exposure to anthracyclines.

Provide supportive care for the treatment of toxicity (e.g., severe neutropenia, severe infectious complications, cardiotoxicity).


Possible secondary AML; risk of refractory AML increases with concomitant DNA-damaging antineoplastics, extensive exposure to cytotoxic drugs, or escalation of anthracycline doses.

The cumulative risk for adjuvant epirubicin therapy-related leukemia is estimated as 0.2 and 0.8% at 3 and 5 years, respectively.


Possible chromosomal damage in human spermatozoa; males should utilize effective contraceptive methods.

Possible irreversible amenorrhea in premenopausal women.

Local Effects

Local pain, severe tissue lesions, and severe local necrosis if extravasation occurs. Must not be given IM or sub-Q (see IV Administration under Dosage and Administration).

Possible venous sclerosis if injected into a small vessel or injected repeatedly into the same vein.

Tumor Lysis Syndrome

Tumor lysis syndrome may result from extensive purine catabolism accompanying rapid cellular destruction; monitor serum uric acid concentration.

Minimize or prevent by adequate hydration, alkalinization of the urine, and/or administration of allopurinol.

Major Toxicities

Hematologic Effects

Possible dose-dependent, reversible leukopenia and/or granulocytopenia (most common acute dose-limiting toxicity).

Leukocyte nadir at day 10–14, with return to baseline by day 21.

Possible severe myelosuppression.

Cardiac Effects

Early (acute) cardiotoxicity (e.g, sinus tachycardia, ECG abnormalities such as nonspecific ST-T wave changes, AV block, ventricular tachycardia) does not predict subsequent development of delayed cardiotoxicity, is rarely of clinical importance, and generally is not an indication for suspension of therapy.

Delayed cardiotoxicity (cardiomyopathy), manifested by reduced left ventricular ejection fraction (LVEF) and CHF, may be life-threatening. Active or occult cardiovascular disease, prior or concomitant irradiation to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic drugs may increase risk.

Monitor LVEF during therapy and discontinue epirubicin at the first sign of impaired cardiac function.

Strictly monitor cardiac function in patients with risk factors for cardiotoxicity; evaluate risk versus benefit of continued therapy in those with impaired cardiac function.

Cardiotoxicity is a cumulative dose-limiting toxicity of the drug. Probability of developing CHF estimated as 0.9, 1.6, and 3.3% at cumulative epirubicin hydrochloride dosages of 550, 700, and 900 mg/m2, respectively. Risk of CHF increases rapidly with total cumulative dose >900 mg/m2; exceed this dose with extreme caution. Possible toxicity at lower cumulative doses, regardless of whether cardiac risk factors are present.

Cardiac effects of epirubicin and other anthracyclines or anthracenediones may be additive.

Cardiovascular Effects

Thrombophlebitis and thromboembolic phenomena, including pulmonary embolism, sometimes fatal, have been reported.

GI Effects

Possible nausea and vomiting; consider prophylaxis with antiemetics.

Possible dose-dependent mucositis (e.g., oral stomatitis, esophagitis); may be severe.


Possible additive cytotoxicity with combined epirubicin and radiation therapy; in clinical studies with epirubicin, radiation therapy was delayed until after completion of the chemotherapy.

Possible inflammatory recall reaction at the site of prior irradiation.

Prophylactic Anti-infective Therapy

In clinical studies, prophylactic anti-infective therapy with co-trimoxazole or a fluoroquinolone was used with the 120-mg/m2 regimen (see Dosage under Dosage and Administration).

Specific Populations


Category D.


Discontinue nursing because of potential risk to nursing infants.

Pediatric Use

Safety and efficacy not established.

Possible increased risk of acute or delayed cardiotoxicity.

Geriatric Use

Careful monitoring for toxicity is recommended.

Hepatic Impairment

Use not recommended in severe impairment. Dosage adjustment for mild to moderate impairment (see Hepatic Impairment under Dosage and Administration).

Common Adverse Effects

Alopecia, nausea/vomiting, myelosuppression (leukopenia, neutropenia, anemia, thrombocytopenia), amenorrhea, mucositis, lethargy, hot flushes (flashes), diarrhea, infection, local effects (e.g., venous irritation), conjunctivitis/keratitis, rash/pruritus, skin changes, fever, anorexia.

Drug Interactions

Antineoplastic Agents

Potential pharmacodynamic interaction (additive pharmacologic and toxic effects).

Cardioactive Agents

Potential pharmacodynamic interaction (potentiation of cardiotoxicity); monitor cardiac function closely with concurrent use of cardioactive drugs that may precipitate CHF (e.g., verapamil).


Potential pharmacokinetic interaction (increased epirubicin concentrations); discontinue during epirubicin therapy.

Hepatoactive Drugs

Potential pharmacologic or pharmacokinetic interaction.

epiRUBicin Pharmacokinetics



Rapidly and widely distributed into body tissues following IV administration. Appears to concentrate in red blood cells; concentrations in whole blood are approximately twice those in plasma. Distributed into milk in rats; not known whether the drug is distributed into milk in humans.

Plasma Protein Binding

Approximately 77% bound to plasma proteins, principally albumin.



Extensively and rapidly metabolized in the liver; also is metabolized in other organs and cells, including erythrocytes. Four main metabolic pathways have been identified. Only the metabolite epirubicinol appears to have cytotoxic activity; however, epirubicinol is unlikely to reach in vivo concentrations sufficient to produce cytotoxic effects.

Elimination Route

Epirubicin and its major metabolites are eliminated in feces via biliary excretion and to a lesser extent in urine.


Plasma concentrations of epirubicin decline in a triphasic manner, with mean half-lives for the α, β, and γ phases of about 3 minutes, 2.5 hours, and 33 hours, respectively.

Special Populations

Clearance is reduced in geriatric women and in patients with hepatic impairment.




Injection, for IV Use

2–8° C. Do not freeze; protect from light. Discard unused solution within 24 hours after initial entry into vial.



Incompatible with any alkaline pH solution (hydrolysis of drug).

Solution CompatibilityHID


Dextrose 3.3% in sodium chloride 0.3%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture Compatibility





Heparin sodium

Irinotecan HCl

Y-Site CompatibilityHID



Manufacturer states that epirubicin hydrochloride should not be mixed with other drugs in the same syringe.

Compatibility in Syringe1HID





Ifosfamide with mesna


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

epiRUBicin Hydrochloride


Dosage Forms


Brand Names



Injection, for IV use only

2 mg/mL (50 and 200 mg)



AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 8, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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