epirubicin hydrochloride

epirubicin hydrochloride

Ellence, Pharmorubicin PMS (CA)

Pharmacologic class: Anthracycline

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category D

FDA Box Warning

• Extravasation during administration causes severe local tissue necrosis; don't give epirubicin hydrochloride by I.M. or subcutaneous route.

• Cardiac toxicity, including fatal congestive heart failure (CHF), may occur either during therapy or months to years after therapy ends. Probability of developing clinically evident CHF is estimated as approximately 0.9% at a cumulative dose of 550 mg/m2, 1.6% at 700 mg/m2, and 3.3% at 900 mg/m2. In adjuvant treatment of breast cancer, maximum cumulative dose used in clinical trials was 720 mg/m2. Risk of developing CHF increases rapidly with increasing total cumulative doses above 900 mg/m2; exceed this cumulative dose only with extreme caution. Active or dormant cardiovascular disease, previous or concurrent radiotherapy to mediastinal or pericardial area, previous anthracycline or anthracenedione therapy, or concurrent use of other cardiotoxic drugs may increase cardiac toxicity risk. Toxicity may occur at lower cumulative doses even if patient has no cardiac risk factors.

• Secondary acute myelogenous leukemia (AML) has been reported in breast cancer patients who have been treated with anthracyclines, including epirubicin. Refractory secondary leukemia is more common when such drugs are given in combination with DNA-damaging antineoplastics, when patients have been heavily pretreated with cytotoxic drugs, or when epirubicin dosage has been escalated. Cumulative risk of developing treatmentrelated AML or myelodysplastic syndrome (MDS), in 7,110 patients with breast cancer who received adjuvant treatment with epirubicin-containing regimens, was estimated as 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years.

• Reduce dosage in patients with hepatic impairment.

• Drug may cause severe myelosuppression.

• Give under supervision of physician experienced in cancer chemotherapy.


Unknown. Forms complex with DNA by intercalation with nucleotide base pairs, causing inhibition of DNA, RNA, and protein synthesis.


Injection: 2 mg/ml, in 5 ml-, 25 ml-, 75 ml-, and 100-ml vials

Powder for injection (lyophilized): 50-mg single-dose vial

Indications and dosages

Adjunctive therapy in patients with axillary-node tumor involvement after resection of primary breast cancer

Adults: 100 to 120 mg/m2 by I.V. infusion over 3 to 5 minutes on first day of each cycle or divided equally in two doses on days 1 and 8 of each cycle; repeat cycle q 3 to 4 weeks for six cycles in conjunction with cyclophosphamide and fluorouracil.

Dosage adjustment

• Hepatic and severe renal impairment
• Hematologic or Grade 3 or 4 non-hematologic toxicity and neutropenic fever

Off-label uses

• Cancer of bladder, lung, nasopharynx, endometrium, and ovaries


• Hypersensitivity to drug, other anthracyclines, or anthracenediones
• Severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias
• Severe hepatic dysfunction
• Baseline neutrophil count below 1,500/mm3
• Previous treatment with anthracyclines up to the maximum cumulative doses


Use cautiously in:
• heart disease, hepatic, or renal disease
• previous or recent radiation therapy
• hyperuricemia
• concurrent use of cimetidine, other cardiotoxic drugs, or live or live-attenuated vaccines
• elderly patients (female patients age 70 and older)
• pregnant or breastfeeding patients
• children.


• Be aware that drug may be given with antibiotics.
• Know that previous anthracycline use must be considered when determining dosage because of increased risk of heart failure.
• Follow facility policy for administration and disposal of carcinogenic drugs.
• Assess blood counts, including absolute neutrophil count, serum creatinine, and liver function before and during each cycle of therapy.
• Consider prophylactic use of antiemetics before administration, particularly when given in conjunction with other emetogenic drugs.

Avoid extravasation. If patient complains of burning or stinging, switch infusion to a different vein.
• Administer premixed solution over 3 to 5 minutes into tubing of free-flowing I.V. line containing dextrose 5% in water or normal saline solution. Don't mix with other drugs in same syringe.
• Direct I.V. push is not recommended because of extravasation risk.
• If patient develops facial flushing or red streak in the vein being infused, slow infusion rate.
• Be aware that refrigerated storage of solution for injection can result in formation of a gelled product. Gelled product will return to a slightly viscous to mobile solution after 2- to a maximum of 4-hour equilibration at controlled room temperature (15° to 25° C [59° to 77° F]).

Adverse reactions

CNS: lethargy

CV: cardiomyopathy, cardiotoxicity, heart failure

EENT: conjunctivitis, keratitis

GI: nausea, vomiting, diarrhea, mucositis

GU: reddish urine, amenorrhea

Hematologic: anemia, leukopenia, neutropenia, thrombocytopenia secondary acute myelogenous leukemia, thrombophlebitis, thromboembolic phenomena

Metabolic: hyperuricemia

Respiratory: pulmonary embolism

Skin: alopecia; rash; pruritus; darkening of soles, palms, or nails

Other: increased appetite, infection, fever, hot flashes, tissue necrosis, injection-related reactions, tumorlysis syndrome


Drug-drug.Cardioactive compounds that could cause heart failure (such as calcium channel blockers): increased risk of heart failure

Cimetidine: increased epirubicin blood level

Live or live-attenuated vaccines: increased risk of serious or fatal infection

Trastuzumab, other cardiotoxic drugs: increased risk of cardiotoxicity

Drug-diagnostic tests.Hemoglobin, neutrophils, platelets, white blood cells: decreased values

Patient monitoring

Monitor vital signs, left ventricular ejection fraction, and cardiovascular status carefully. Watch for signs and symptoms of cardiomyopathy and heart failure.
• Assess nutritional status and hydration in light of GI adverse effects.

Monitor CBC with white cell differential and watch for signs and symptoms of blood dyscrasias.
• Check temperature. Stay alert for fever and other signs or symptoms of infection.

Consider the possibility of tumor lysis syndrome in potentially susceptible patients and monitor serum uric acid, potassium, calcium, phosphate, and creatinine levels immediately after initial chemotherapy. Be aware that hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome.
• Continue to monitor serum total bilirubin, AST, and serum creatinine levels during treatment.

Patient teaching

• Inform patient that drug may cause tissue damage at injection site. Tell him to report pain, burning, or swelling.

Instruct patient to immediately report sudden weight gain, swelling, or shortness of breath.

Tell patient to promptly report unusual bruising or bleeding, fever, or signs and symptoms of infection or tumor lysis syndrome.
• Advise patient to avoid receiving live vaccines while taking this drug.
• Explain that drug will cause hair loss but that hair should grow back within a few months after therapy.
• Advise female patient that drug may cause premature menopause or permanent cessation of menses.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

epirubicin hydrochloride

An antibiotic that is an isomer of doxorubicin, used in the treatment of breast cancer.
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References in periodicals archive ?
In the other 33 patients, doxorubicin hydrochloride or epirubicin hydrochloride (10-20 mg/m2) were injected every 2-4 weeks in a "one-shot" manner.
In October 2007, the Company received tentative approval for Irinotecan Hydrochloride Injection and approvals for Epirubicin Hydrochloride Injection (in four dosage forms), liquid and lyophilized Fludarabine Phosphate.
Food and Drug Administration (FDA) to market Epirubicin hydrochloride injection in four dosage forms.
Food and Drug Administration has granted final approval for the Company's Abbreviated New Drug Application (ANDA) for Epirubicin Hydrochloride Injection, 2 mg/mL.