learn [50,000/mm:<250/mm 3 , 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. 1 Delay day-1 chemotherapy in subsequent cycles until platelet counts are ≥100,000/mm 3 , ANCs are ≥1500/mm 3 , and nonhematologic toxicities have recovered to grade 1 or better. 1 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/mm 3 , respectively. 1 If day-8 platelet counts or ANCs are> <75,000 or 1000/mm 3 , respectively, or grade 3 or 4 nonhematologic toxicity has occurred, omit day-8 dose of each drug. 1 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. 1 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. 1 Epirubicin is not recommended in patients with severe hepatic impairment. 1 Renal Impairment Consider dosage reduction if S cr is >5 mg/dL; not studied in those undergoing dialysis. 1 Bone Marrow Impairment Consider decreasing dosage for the initial cycle to 75 90 mg/m 2 in patients with bone marrow impairment (e.g., extensive pretreatment, preexisting myelosuppression, neoplastic bone marrow infiltration). 1 Cautions for Ellence Contraindications Known hypersensitivity to epirubicin, other anthracyclines, anthracenediones, or any ingredient in the formulation. 1 Baseline neutrophil count> <1500/mm 3 . 1 Severe myocardial or hepatic impairment or recent myocardial infarction. 1 Previous anthracycline therapy up to the maximum cumulative dose. 1 Warnings/Precautions Warnings Adequate Patient Evaluation and Monitoring Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy. 1 Patients must have recovered from acute toxicities (e.g., stomatitis, neutropenia, thrombocytopenia, generalized infections) of prior cytotoxic therapy before starting treatment with epirubicin. 1 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. 1 Provide supportive care for the treatment of toxicity (e.g., severe neutropenia, severe infectious complications, cardiotoxicity). 1 Carcinogenicity Possible secondary AML; risk of refractory AML increases with concomitant DNA-damaging antineoplastics, extensive exposure to cytotoxic drugs, or escalation of anthracycline doses. 1 The cumulative risk for adjuvant epirubicin therapy-related leukemia is estimated as 0.2 and 0.8% at 3 and 5 years, respectively. 1 Fertility Possible chromosomal damage in human spermatozoa; males should utilize effective contraceptive methods. 1 Possible irreversible amenorrhea in premenopausal women. 1 Local Effects Local pain, severe tissue lesions, and severe local necrosis if extravasation occurs. 1 Must not be given IM or sub-Q (see IV Administration under Dosage and Administration). 1 Possible venous sclerosis if injected into a small vessel or injected repeatedly into the same vein. 1 Tumor Lysis Syndrome Tumor lysis syndrome may result from extensive purine catabolism accompanying rapid cellular destruction; monitor serum uric acid concentration. 1 Minimize or prevent by adequate hydration, alkalinization of the urine, and/or administration of allopurinol. 1 Major Toxicities Hematologic Effects Possible dose-dependent, reversible leukopenia and/or granulocytopenia (most common acute dose-limiting toxicity). 1 Leukocyte nadir at day 10 14, with return to baseline by day 21. 1 Possible severe myelosuppression. 1 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. 1 Delayed cardiotoxicity (cardiomyopathy), manifested by reduced left ventricular ejection fraction (LVEF) and CHF, may be life-threatening. 1 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. 1 Monitor LVEF during therapy and discontinue epirubicin at the first sign of impaired cardiac function. 1 Strictly monitor cardiac function in patients with risk factors for cardiotoxicity; evaluate risk versus benefit of continued therapy in those with impaired cardiac function. 1 Cardiotoxicity is a cumulative dose-limiting toxicity of the drug. 1 Probability of developing CHF estimated as 0.9, 1.6, and 3.3% at cumulative epirubicin hydrochloride dosages of 550, 700, and 900 mg/m 2 , respectively. 1 Risk of CHF increases rapidly with total cumulative dose >900 mg/m 2 ; exceed this dose with extreme caution. 1 Possible toxicity at lower cumulative doses, regardless of whether cardiac risk factors are present. 1 Cardiac effects of epirubicin and other anthracyclines or anthracenediones may be additive. 1 Cardiovascular Effects Thrombophlebitis and thromboembolic phenomena, including pulmonary embolism, sometimes fatal, have been reported. 1 GI Effects Possible nausea and vomiting; consider prophylaxis with antiemetics. 1 Possible dose-dependent mucositis (e.g., oral stomatitis, esophagitis); may be severe. 1 Irradiation Possible additive cytotoxicity with combined epirubicin and radiation therapy; in clinical studies with epirubicin, radiation therapy was delayed until after completion of the chemotherapy. 1 Possible inflammatory recall reaction at the site of prior irradiation. 1 Prophylactic Anti-infective Therapy In clinical studies, prophylactic anti-infective therapy with co-trimoxazole or a fluoroquinolone was used with the 120-mg/m 2 regimen (see Dosage under Dosage and Administration). 1 Specific Populations Pregnancy Category D. 1 Lactation Discontinue nursing because of potential risk to nursing infants. 1 Pediatric Use Safety and efficacy not established. 1 Possible increased risk of acute or delayed cardiotoxicity. 1 Geriatric Use Careful monitoring for toxicity is recommended. 1 Hepatic Impairment Use not recommended in severe impairment. 1 Dosage adjustment for mild to moderate impairment (see Hepatic Impairment under Dosage and Administration). 1 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. 1 Interactions for Ellence Antineoplastic Agents Potential pharmacodynamic interaction (additive pharmacologic and toxic effects). 1 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). 1 Cimetidine Potential pharmacokinetic interaction (increased epirubicin concentrations); discontinue during epirubicin therapy. 1 Hepatoactive Drugs Potential pharmacologic or pharmacokinetic interaction. 1 Ellence Pharmacokinetics Distribution Extent Rapidly and widely distributed into body tissues following IV administration. 1 Appears to concentrate in red blood cells; concentrations in whole blood are approximately twice those in plasma. 1 Distributed into milk in rats; not known whether the drug is distributed into milk in humans. 1 Plasma Protein Binding Approximately 77% bound to plasma proteins, principally albumin. 1 Elimination Metabolism Extensively and rapidly metabolized in the liver; also is metabolized in other organs and cells, including erythrocytes. 1 Four main metabolic pathways have been identified. 1 Only the metabolite epirubicinol appears to have cytotoxic activity; however, epirubicinol is unlikely to reach in vivo concentrations sufficient to produce cytotoxic effects. 1 Elimination Route Epirubicin and its major metabolites are eliminated in feces via biliary excretion and to a lesser extent in urine. 1 Half-life 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. 1 Special Populations Clearance is reduced in geriatric women and in patients with hepatic impairment. 1 Stability Storage Parenteral Injection, for IV Use 2 8 C. 1 Do not freeze; protect from light. 1 Discard unused solution within 24 hours after initial entry into vial. 1 HID Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Incompatible with any alkaline pH solution (hydrolysis of drug). 1 Solution Compatibility HID Compatible Dextrose 3.3% in sodium chloride 0.3% Dextrose 5% in water Ringer s injection, lactated Sodium chloride 0.9% Drug Compatibility Admixture Compatibility Compatible Ifosfamide Incompatible Fluorouracil Heparin sodium Irinotecan HCl Y-Site CompatibilityHID Compatible Oxaliplatin Manufacturer states that epirubicin hydrochloride should not be mixed with other drugs in the same syringe. 1 Compatibility in Syringe1HID Compatible Ifosfamide Incompatible Fluorouracil Ifosfamide with mesna Actions Pharmacologic actions similar to those of daunorubicin and doxorubicin. 1 2 3 4 Intercalates between base pairs causing template disordering and steric obstruction; thereby inhibits DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis 1 2 4 and triggers DNA cleavage by topoisomerase II. 1 2 3 4 Also inhibits DNA helicase and generates cytotoxic free radicals. 1 2 3 4 Compared with doxorubicin, is more lipophilic, may have improved therapeutic index, 3 4 and is less toxic; 2 3 similar spectrum of activity against a wide variety of solid tumors and hematologic malignancies, and complete cross-resistance. 2 3 4 Advice to Patients Importance of recognizing and reporting adverse effects of epirubicin, including GI and myelosuppressive effects (and related precautions), infectious complications, CHF symptoms, and injection site pain. 1 Risk of irreversible myocardial toxicity and leukemia. 1 Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy, advise pregnant women of risk to the fetus, and advise males to utilize effective contraception during therapy. 1 Inform women of risk of irreversible amenorrhea or premature menopause. 1 Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses. 1 Probable alopecia; reddish appearance of urine for 1 2 days (harmless). 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations 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 Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection, for IV use only 2 mg/mL (50 and 200 mg) Ellence Pharmacia AHFS DI Essentials. Copyright 2017, Selected Revisions July 8, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Pharmacia. Ellence (epirubicin hydrochloride) injection prescribing information. Kalamazoo, MI; 2002 Jan. 2. Coukell AJ, Faulds D. Epirubicin: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs . 19997; 53:453-82. 3. Bonadonna G, Giannia L, Santoro A et al. Drugs ten years later: epirubicin. Ann Oncol . 1993; 4:359-69. [PubMed 8353070] 4. Pharmacia & Upjohn Co. Oncologic Drugs Advisory Committee (ODAC) brochure: NDA 21-010, epirubicin hydrochloride injection, amendment 019. Kalamazoo, MI; 1999 Jun 7. 5. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther . 2000; 42:83-92. [PubMed 10994034] HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2013:446-8. Next Interactions Print this page Add to My Med List More about Ellence (epirubicin) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Generic Availability Drug class: antibiotics/antineoplastics Consumer resources Ellence Ellence (Advanced Reading) Professional resources Ellence (FDA) Epirubicin Hydrochloride (AHFS Monograph) Related treatment guides Breast Cancer, Adjuvant> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Pfizer Inc. Drug Class Antibiotics / antineoplastics Related Drugs Breast Cancer, Adjuvant tamoxifen , letrozole , Femara , Taxol , Herceptin , paclitaxel , trastuzumab , Nolvadex , epirubicin , Nerlynx , neratinib , Soltamox , More... Ellence Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } it's also
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