Epirubicin hydrochloride is available as a clear, red, preservative-free, ready-to-use 2-mg/mL solution in single-use 25- and 100-mL vials containing 50 and 200 mg of drug, respectively.3377 The solution also contains sodium chloride and water for injection.3377 The pH has been adjusted with hydrochloric acid and/or sodium hydroxide.3377
pH
Adjusted to 3.3377
Trade Name(s)
Ellence
Epirubicin hydrochloride is administered slowly by intravenous infusion into the tubing of a freely running intravenous infusion of sodium chloride 0.9% or dextrose 5%.3377 The manufacturer states that initial therapy at the recommended starting dosage generally should be infused over 15 to 20 minutes.3377 For patients receiving reduced dosages (e.g., due to organ dysfunction and/or dosage modification for toxicity), the infusion time may be proportionally decreased; however, the drug should not be infused over less than 3 minutes.3377 Administration by direct push injection is not recommended because of the risk of extravasation.3377
Extravasation may occur even in the presence of adequate blood return upon needle aspiration.3377 Extravasation may cause local pain, severe tissue lesions (e.g., vesication, severe cellulitis), and necrosis and should be avoided.3377 Burning or stinging may indicate perivenous infiltration, which requires immediately terminating the infusion and restarting it in another vein.3377 Perivenous infiltration also may occur without pain.3377 Venous sclerosis may result from injection of the drug into a small vessel or from repeated injection into the same vein.3377 Facial flushing and erythematous streaking along the vein may result from excessively rapid administration and may precede local phlebitis or thrombophlebitis.3377 Decreasing the duration of infusion of the drug proportionally with an indicated dosage reduction is intended to reduce the risk of thrombosis or perivenous extravasation, which could in turn reduce the risk of severe cellulitis, vesication, or tissue necrosis.3377 Infusion of the drug into veins occurring over joints or in extremities with compromised venous or lymphatic drainage should be avoided if possible.3377 Epirubicin hydrochloride must not be administered by intramuscular or subcutaneous injection.3377
As with other toxic drugs, applicable special handling and disposal procedures for epirubicin hydrochloride should be followed.3377
Intact vials should be stored at 2 to 8°C and protected from freezing and exposure to light.3377 Although vials should be stored under refrigeration, manufacturers note that refrigeration of epirubicin hydrochloride injection can result in the formation of a gelled product; however, the gelled product will return to a slightly viscous to mobile solution after 2 to 4 hours (maximum) at a controlled room temperature of 15 to 25°C.3377 Epirubicin hydrochloride solution should be visually inspected for particulate matter and discoloration prior to administration.3377 Vials are for single use only and any unused portion should be discarded.3377 Manufacturers recommend that any unused solution from the single-dose vials be discarded within 24 hours after initial puncture of the vial stopper.3377
The manufacturer states that the drug should not be mixed with other drugs in the same syringe.3377
pH Effects
Epirubicin hydrochloride stability is pH dependent. The drug becomes progressively more stable at acid pH, with maximum stability at pH 4 to 5.1007; 1460 Prolonged contact of epirubicin hydrochloride with any solution having an alkaline pH should be avoided because of the resulting hydrolysis of the drug.3377
Light Effects
Although epirubicin hydrochloride is photosensitive, no special precautions are necessary to protect solutions containing epirubicin hydrochloride 500 mcg/mL or greater during intravenous administration,1463 even over periods extending to 14 days in room light.2081
Syringes
Epirubicin hydrochloride 2 mg/mL in sterile water for injection was stable for at least 43 days at 4°C in Plastipak (Becton Dickinson) plastic syringes.1460
Epirubicin hydrochloride 0.5 mg/mL in sodium chloride 0.9% was reported to be stable for at least 28 days at 4 and 20°C when stored in plastic syringes.1564
Epirubicin hydrochloride 2 mg/mL in sodium chloride 0.9% in 50-mL polypropylene syringes with blind luer hubs was stored at 25°C both in light and dark and at 4°C in dark. About 2 to 4% loss occurred in 14 days at 25°C whether in light or dark. No loss was found after 180 days of refrigerated storage.2081
Epirubicin hydrochloride (Farmorubicine, Pfizer) lyophilized powder formulation containing methylparaben and lactose was reconstituted with sodium chloride 0.9% to a final concentration of 8.33 mg/mL and stored as 6 mL in 50-mL brown polypropylene syringes (Becton Dickinson) with polypropylene caps protected from light.3378 The solution was reported to be physically and chemically stable, retaining at least 95% of the initial concentration for 72 hours at 4°C with or without additional storage for 4 hours at 22°C.3378
Sorption
Although epirubicin hydrochloride was initially reported to undergo sorptive losses to PVC containers, subsequent studies have shown no loss to glass, PVC, and high-density polyethylene containers, PVC, polyethylene, and polybutadiene infusion sets, and polypropylene syringes.1460; 1577; 1700
Filtration
Epirubicin hydrochloride 50 mg/1000 mL in dextrose 5% and sodium chloride 0.9% was infused over 24 hours and exhibited a drug loss during the initial period of filtration through cellulose ester and nylon filters; however, the concentrations returned to expected levels within minutes, and the total amount of drug lost was deemed negligible.1577
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