epirubicin

ROUTE	ONSET	PEAK	DURATION
IV	unknown	10–14 days	21 days

Contraindicated in:

Hypersensitivity to epirubicin, other anthracyclines, or related compounds;
Baseline neutrophil count <1500 cells/mm³;
HF;
Recent MI;
Severe arrhythmias
Previous treatment with anthracyclines up to the maximum cumulative dose;
Severe hepatic impairment;
Concurrent cimetidine therapy;
OB: May cause fetal harm (avoid use during 1st trimester);
Lactation: Lactation

Use Cautiously in:

Cardiovascular disease, prior or concomitant radiation therapy to mediastinal or pericardial area, previous therapy with anthracyclines, or concomitant use of cardiotoxic drugs (↑ risk of cardiotoxicity);
Severe renal impairment (serum creatinine >5 mg/dL); consider ↓ dose;
Hepatic impairment (dose ↓ recommended for bilirubin >1.2 mg/dL or AST >2.2–4 times upper limit of normal);
Depressed bone marrow reserve;
OB: Use during 2nd or 3rd trimester only if potential maternal benefit justifies potential fetal risk;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established; risk of acute cardiotoxicity and chronic HF;
Geri: risk of toxicity in females 70 yr.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, heart block, HF (DOSE-RELATED), thromboembolism, ventricular tachycardia

Derm: alopecia, flushing, itching, photosensitivity, radiation-recall reaction, rash, skin/nail hyperpigmentation

Endo: gonadal suppression

GI: nausea, vomiting, anorexia, diarrhea, mucositis

GU: ↓fertility, ↓sperm production, amenorrhea

Hemat: anemia, LEUKOPENIA, thrombocytopenia, treatment-related leukemia/myelodysplastic syndromes

Local: injection site reactions, phlebitis at IV site, tissue necrosis

Metab: hot flashes, hyperuricemia

Neuro: lethargy

Misc: ANAPHYLAXIS, INFECTION

Interactions ⬆ ⬇

Drug-drug:

Cimetidine↑ blood levels and risk of serious toxicity; avoid concurrent use.
Additive hematologic and gastrointestinal toxicity with other antineoplastics or radiation therapy.
Use with other cardiotoxic drugs may ↑ risk of cardiotoxicity; avoid concurrent use.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
Trastuzumab may ↑ risk of cardiotoxicity; avoid use of epirubicin for up to 7 mo after discontinuing trastuzumab.

Route/Dosage ⬆ ⬇

IV (Adults ): 100–120 mg/m² repeated in 3–4 wk cycles (total dose may be given on Day 1 or split and given in equally divided doses on Day 1 and Day 8 of each cycle) (combination regimens may employ concurrent 5-fluorouracil and cyclophosphamide).

Hepatic Impairment

IV (Adults ): Bilirubin 1.2–3 mg/dL or AST 2–4x ULN: use 50% of recommended starting dose; Bilirubin >3 m g/dL or AST >4x ULN: use 25% of recommended starting dose.

Availability ⬆ ⬇

(Generic available)

Solution for injection: 2 mg/mL

Assessment ⬆ ⬇

Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Severe nausea and vomiting may occur. Administer parenteral antiemetic agents 30–45 min prior to therapy and routinely around the clock for next 24 hr as indicated. Monitor amount of emesis and notify health care professional if emesis exceeds guidelines to prevent dehydration.
Measure cardiac function, using ECG and a multigated radionuclide angiography (MUGA) scan or an ECHO, prior to therapy. Perform repeated evaluations of left ventricular ejection fraction during therapy. Monitor for development of signs of cardiac toxicity, which may occur early (ST-T wave changes, sinus tachycardia, and extrasystoles) or late (may occur mo to yr after termination of therapy). Delayed cardiac toxicity is characterized by cardiomyopathy, tachycardia, peripheral edema, dyspnea, rales/crackles, weight gain, hepatomegaly, ascites, pleural effusion. Toxicity is usually dependent on cumulative dose.
Assess injection site frequently for redness, irritation, or inflammation. Burning or stinging during infusion may indicate infiltration and infusion should be discontinued and restarted in another vein. Epirubicin is a vesicant but may infiltrate painlessly even if blood returns on aspiration of infusion needle. Severe tissue damage may occur if epirubicin extravasates. If extravasation occurs, stop infusion immediately, restart, and complete dose in another vein.
Assess oral mucosa frequently for development of stomatitis (pain, burning, erythema, ulcerations, bleeding, infection). Increased dosing interval and/or decreased dosing is recommended if lesions are painful or interfere with nutrition.

Lab Test Considerations:

Obtain negative pregnancy test before starting therapy.Monitor CBC and differential before and during each cycle of therapy. Epirubicin should not be administered to patients with a baseline neutrophil count <1500 cells/mm³. The WBC nadir occurs 10–14 days after administration, and recovery usually occurs by the 21st day. Severe thrombocytopenia and anemia may also occur.
- Monitor renal (BUN and creatinine) and hepatic (AST, ALT, LDH, and serum bilirubin) function prior to and periodically during therapy. Dose reduction is required for bilirubin >1.2 m g/dL, AST 2–4 times the upper limit of normal, or serum creatinine >5 m g/dL.

Implementation ⬆ ⬇

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations and infusion pump settings. Epirubicin should be administered only under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
Do not confuse epirubicin with eribulin.
Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
- Administer prophylactic anti-infective therapy with trimethoprim/sulfamethoxazole or a fluoroquinolone and antiemetic therapy prior to administration of epirubicin.
- Do not administer SUBQ or IM.

IV Administration:

Intermittent Infusion: Diluent: Administer undiluted. Solution is clear red. Use epirubicin within 24 hr of penetration of rubber stopper. Discard unused solution.Concentration: 2 mg/mL.
Rate: Administer initial dose of 100–120 mg/m² over 15–20 min through free-flowing infusion of 0.9% NaCl or D5W. Lower doses may be infused for shorter periods, but not less than over 3 min. Do not administer via IV push. Facial flushing and erythema along involved vein frequently occur when administration is too rapid. Venous sclerosis may result from injection into a small vein or repeated injections into the same vein. Avoid veins over joints or in extremities with compromised venous or lymphatic drainage.

Patient/Family Teaching ⬆ ⬇

Instruct patient to notify health care professional promptly if fever; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should be cautioned not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
Instruct patient to report pain at injection site immediately.
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush, rinse mouth with water after eating and drinking, and confer with health care professional if mouth pain interferes with eating. Pain may require treatment with opioid analgesics. Patients usually recover by the third wk of therapy.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of alcohol or OTC medications and herbal products, especially cold preparations, without consulting health care professional, especially cimetidine.
Instruct patient to notify health care professional immediately if vomiting, dehydration, fever, evidence of infection, symptoms of HF, or pain at injection site occurs. Patients should be informed of the risk of irreversible cardiac damage and treatment-related leukemia.
Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
Instruct patient not to receive any vaccinations without advice of health care professional.
Inform patient that medication may cause urine to appear red for 1–2 days.
Instruct patient to notify health care professional if skin irritation occurs at site of previous radiation therapy. May cause hyperpigmentation of the skin and nails. Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Rep: May have teratogenic effects. Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose of therapy and to avoid breast feeding for at least 7 days after last dose of epirubicin. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose of therapy and to use condoms during and for at least 7 days after last dose of epirubicin. Inform females and males that epirubicin may cause permanent loss of fertility.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇