Names and pronunciation
(ep-ih-roo′bi-sin) Ellence, Pharmorubicin
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Drug reference
(ep-ih-roo′bi-sin) Ellence, Pharmorubicin
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Func. class.: Antineoplastic, antibiotic
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Chem. class.: Anthracycline
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Do not confuse: epirubicin/eribulin
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ACTION: Inhibits DNA synthesis pri- marily; replication is decreased by binding to DNA, which causes strand splitting; maximum cytotoxic effects at S and for G2 phases; a vesicant
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USES: Adjuvant therapy for breast can- cer with axillary node involvement after resection
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Unlabeled uses: Used in combination for treatment of advanced forms of can- cer: bladder, gastric, head and neck, hepatocellular, lung, ovarian, multiple myeloma, soft tissue sarcoma
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CONTRAINDICATIONS: Preg- nancy, breastfeeding; hypersensitivity to product, anthracyclines, anthracenediones; baseline neutrophil count <1500 cells/ mm3, severe myocardial insufficiency, recent MI, heart failure, cardiomyopathy
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Black Box Warning: Severe hepatic dis- ease, IM/SUBCUT use Precautions: Children, geriatric patients, cardiac/renal/hepatic disease, accidental exposure, angina, dental dis- ease, herpes, hyperkalemia, hyperphos- phatemia, hypertension, hyperuricemia, hypocalcemia, infection, infertility, tumor lysis syndrome, ventricular dysfunction, previous anthracycline use Black Box Warning: Bone marrow de- pression (severe), heart failure, extrava- sation, secondary malignancy, requires an experienced clinician Black Box Warning: To be used by a clinician experienced in giving cytotoxic products Black Box Warning: Do not use IM/SUB- CUT, severe tissue necrosis, give IV only, a vesicant; if extravasation occurs, stop and complete via another vein, preferably in another limb; avoid infusion into veins over joints or in extremities with compro- mised venous or lymphatic drainage • Rapid injection can cause facial flush- ing or erythema along the vein; avoid administration time of <3 min • Product should be given to those with neutrophils ≥1500/mm3, platelet count ≥100,000/mm3, and nonhematologic tox- icities recovered to ≤grade 1 • When refrigerated, the preservative- free, ready-to-use solution can form a gelled product and will return to solution after 2-4 hr at room temperature • Visually inspect for particulate matter and discoloration prior to use IV route • Double-check dose and product; fatali- ties have occurred with wrong dose or product • Give anti-infectives prior to use of this product • Use cytotoxic handling procedures; pregnant women must not handle product • Reconstitute 50 mg and 200 mg pow- der for injection vials with 25 mL and 100 mL, respectively, of sterile water for injection (2 mg/mL); shake vigorously for up to 4 min; reconstituted solutions are stable for 24 hr when stored refriger- ated and protected from light or at room temperature in normal light • Solution can be further diluted with sterile water for injection IV INJ route • Give doses of 100-120 mg/m2 into tubing of a freely flowing 0.9% sodium chloride (NS) or D5W IV infusion over 15-20 min; the infusion time may be de- creased proportionally in those who re- quire lower doses; infusion times <3 min are not recommended • Direct injection into the vein is not recommended because of the risk of ex- travasation; avoid use with any solution of alkaline pH because hydrolysis will occur IV INFUSION route • Dilute dose in 0.9% sodium chloride (NS) or D5W, infuse over 30-60 min, avoid use with any solution of alkaline pH because hydrolysis will occur compatibilities: Alemtuzumab, Y-site alfentanil, amifostine, amikacin, aminoca- proic acid, anidulafungin, argatroban, atracurium, aztreonam, bivalirudin, bleo- mycin, bumetanide, buprenorphine, butorphanol, calcium chloride/gluconate, CARBOplatin, caspofungin, ceFAZolin, cefotaxime, ceftizoxime, chlorproMAZINE, cimetidine, ciprofloxacin, cisatracurium, CISplatin, clindamycin, cyclophosphamide, cycloSPORINE, DAPTOmycin, dexrazox- ane, digoxin, diltiazem, diphenhydrAMINE, DOBUTamine, DOCEtaxel, dolasetron, DOPamine, doxacurium, doxycycline, dro- peridol, enalaprilat, ePHEDrine, EPINEPH- rine, ertapenem, erythromycin, etoposide, famotidine, fenoldopam, fentaNYL, flucon- azole, gatifloxacin, gemcitabine, gentami- cin, granisetron, haloperidol, hydrocorti- sone, HYDROmorphone, hydrOXYzine, ifosfamide, imipenem-cilastatin, inamri- none, insulin (regular), isoproterenol, labetalol, levofloxacin, levorphanol, lidocaine, linezolid, LORazepam, mannitol, meperidine, mesna, methotrexate, meto- clopramide, metoprolol, metroNIDAZOLE, midazolam, milrinone, minocycline, mito- MYcin, mivacurium, morphine, moxifloxa- cin, nalbuphine, naloxone, nesiritide, niCARdipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ofloxacin, ondansetron, oxaliplatin, PACLitaxel, palo- E nosetron, pamidronate, pancuronium, pentamidine, pentazocine, phenylephrine, potassium chloride, procainamide, pro- chlorperazine, promethazine, propranolol, quinupristin-dalfopristin, ranitidine, remi- fentanil, rocuronium, sodium acetate, succinylcholine, SUFentanil, tacrolimus, teniposide, theophylline, thiotepa, tigecy- cline, tirofiban, tobramycin, trimetho benzamide, vancomycin, vasopressin, vecuronium, verapamil, vinBLAStine, vin- CRIStine, vinorelbine, voriconazole, zido vudine, zoledronic acid Black Box Warning: Bone marrow de- pression (severe): CBC, differential, platelet count weekly; withhold product if baseline neutrophil ≤1500/mm3; leukocyte nadir oc- curs 10-14 days after administration, recov- ery by day 21; notify prescriber of results; assess for bleeding: hematuria, guaiac, bruising, or petechiae, or mucosa, orifices • Infection: treat prior to receiving this product if regimens >120 mg/m2, prophy- lactic antibiotics should be given (trimeth oprim-sulfamethoxazole or a quinolone) • Blood, urine uric acid levels; swelling, joint pain primarily in extremities; patient should be well hydrated to prevent urate deposits • Renal disease: BUN, serum uric acid, urine CCr, electrolytes prior to, during therapy; I&O ratio; report fall in urine output to <30 mL/hr; dosage adjustment needed if serum creatinine >5 mg/dL • Increase fluid intake to 2-3 L/day to prevent urate, calculi formation Black Box Warning: Hepatic studies prior to, during therapy: bilirubin, AST, ALT, alkaline phosphatase as needed or monthly Black Box Warning: Heart failure: B/P, pulse, character, rhythm, rate, ABGs, ECG, LVEF, MUGA scan, or ECHO; watch for ST-T wave changes, low QRS and T, possible dysrhythmias (sinus tachycar- dia, heart block, PVCs); identify cumula- tive amount of anthracycline received (lifetime); reactions that follow may be delayed; assess for dyspnea, tachycardia, peripheral edema, rales/crackles, ascites • Effects of alopecia on body image; discuss feelings about body changes Black Box Warning: Extravasation (vesicant): local irritation, pain, burning, necrosis at injection site; discontinue and start at another site. • Stomatitis: oral mucosa for ulcer- ation, burning, bleeding; may lead to in- ability to eat and swallow • GI symptoms: frequency of stools, cramping • Pregnancy/breastfeeding: Women of reproductive potential should avoid becom- ing pregnant during therapy and should be advised to use effective contraceptive methods. If a woman becomes pregnant during therapy, she should be advised of the potential risks to the fetus. There is poten- tial for male-mediated teratogenicity. Men with sexual partners of reproductive poten- tial should use effective contraceptive methods during and after therapy. Men or women who receive this product may have a risk of infertility. Women treated may de- velop irreversible amenorrhea or premature menopause; discontinue breastfeeding or discontinue product Black Box Warning: That irreversible myocardial damage, leukopenia, meno- pause may occur • To report rapid heartbeat, trouble breath- ing, fever, nausea, vomiting, oral sores • To report pain at site immediately • Pregnancy/breastfeeding: that con- traceptive measures are recommended during therapy and for 4 mo thereafter for men and women; not to breastfeed
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SIDE EFFECTS CV: Increased B/P, sinus tachycardia, PVCs, chest pain, bradycardia, extrasys- toles, cardiomyopathy GI: Nausea, vomiting, anorexia, muco- sitis, diarrhea GU: Amenorrhea, hot flashes, hyperuri- cemia, red urine HEMA: Thrombocytopenia, leukopenia, anemia, neutropenia, secondary AML INTEG: Rash, necrosis, pain at injec- tion site, reversible alopecia MISC: Infection, febrile neutropenia, lethargy, fever, conjunctivitis, tumor lysis syndrome
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INTERACTIONS • Give epiRUBicin prior to PACLitaxel if both are given Increase: toxicity—other antineoplastics or radiation, cimetidine Increase: ventricular dysfunction, HF— trastuzumab Increase: heart failure—calcium channel blockers Decrease: antibody response—live virus vaccine
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DOSAGE AND ROUTES • Adult: IV 100 mg/m2 on day 1 with fluorouracil and cyclophosphamide (FEC regimen) every 21 days × 6 cycles or 60 mg/m2 on days 1 and 8 with oral cyclo- phosphamide and fluorouracil every 28 days × 6 cycles Dosage adjustments based on hematologic and nonhematologic toxicities • Nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or grades 3/4 nonhematologic toxicities: Day 1 dose in subsequent cycles should be reduced by 25% of the previous dose • For patients receiving divided-dose epirubicin (days 1 and 8): Day 8 dose should be reduced by 25% of the day 1 dose if the platelet counts are 75,000- 100,000/mm3 and the ANC is 1000-1499/ mm3; if day 8 platelet counts are <75,000/ mm3, ANC <1000/mm3, or grade 3/4 non- hematologic toxicity has occurred, omit the day 8 dose Hepatic dose • Adult: IV Bilirubin 1.2-3 mg/dL or AST 2-4 × normal upper limit, 50% of start- ing dose; bilirubin >3-5 mg/dL or AST >4 × normal upper limit, 25% of starting dose
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Available forms: Solution for injection 2 mg/mL (250 mg/25 mL, 200 mg/100 mL)
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Administer: • Antiemetic 30-60 min prior to product to prevent vomiting
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Assess:
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That hair may be lost during treat- ment; that wig or hairpiece may make patient feel better; that new hair may be different in color, texture; new hair growth occurs in ≤3 mo after treat- ment • To avoid crowds, persons with infec- tions when granulocyte count is low • To avoid vaccinations because reac- tions may occur; to avoid cimetidine during therapy • That urine may appear red for 2 days • To avoid OTC medications, supple- ments unless approved by prescriber
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PHARMACOKINETICS Triphasic pattern of elimination; half-life 3 min, 1 hr, 30 hr; metabolized by liver, extensively; crosses placenta; widely dis- tributed to RBCs, excreted in urine, bile, breast milk
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• Adult: IV 100 mg/m2 on day 1 with fluorouracil and cyclophosphamide (FEC regimen) every 21 days × 6 cycles or 60 mg/m2 on days 1 and 8 with oral cyclo- phosphamide and fluorouracil every 28 days × 6 cycles Dosage adjustments based on hematologic and nonhematologic toxicities
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• Nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or grades 3/4 nonhematologic toxicities: Day 1 dose in subsequent cycles should be reduced by 25% of the previous dose
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• For patients receiving divided-dose epirubicin (days 1 and 8): Day 8 dose should be reduced by 25% of the day 1 dose if the platelet counts are 75,000- 100,000/mm3 and the ANC is 1000-1499/ mm3; if day 8 platelet counts are <75,000/ mm3, ANC <1000/mm3, or grade 3/4 non- hematologic toxicity has occurred, omit the day 8 dose Hepatic dose
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• Adult: IV Bilirubin 1.2-3 mg/dL or AST 2-4 × normal upper limit, 50% of start- ing dose; bilirubin >3-5 mg/dL or AST >4 × normal upper limit, 25% of starting dose
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