Acyclovir sodium is available as a 50 mg/mL concentrate for injection in 10- or 20-mL single-dose, preservative-free vials containing 500 mg or 1 g of acyclovir, respectively, as the sodium salt in water for injection.3795 The concentrate must be diluted in an appropriate infusion solution prior to intravenous infusion.3795 A diluted concentration of approximately 7 mg/mL or less is recommended.3795
Acyclovir sodium also may be available as a lyophilized powder in vials containing 500 mg or 1 g of acyclovir as the sodium salt.3796 Reconstitute the 500-mg vial with 10 mL and the 1-g vial with 20 mL of sterile water for injection to yield a solution containing acyclovir 50 mg/mL; shake well to ensure complete dissolution.3796 Do not use bacteriostatic water for injection containing parabens or benzyl alcohol for reconstitution.3796 The reconstituted solution must be diluted in an appropriate infusion solution prior to intravenous infusion.3795 A diluted concentration of approximately 7 mg/mL or less is recommended.3795
Equivalency
Acyclovir sodium 54.9 mg is equivalent to 50 mg of acyclovir.3795
pH
The concentrate for injection has a pH ranging from 10.85 to 11.5.3795
The reconstituted solution has a pH of approximately 11.3796
Osmolality
The osmolality of acyclovir sodium 500 mg was calculated for the following dilutions:1054
| Osmolality (mOsm/kg) | ||
|---|---|---|
| Diluent | 50 mL | 100 mL |
| Dextrose 5% | 316 | 289 |
| Sodium chloride 0.9% | 342 | 316 |
The osmolality of acyclovir sodium 7 mg/mL was determined to be 278 mOsm/kg in dextrose 5% and 299 mOsm/kg in sodium chloride 0.9%.1375
In another study, the osmolality of acyclovir sodium 5 mg/mL (GlaxoSmithKline) in sodium chloride 0.9% was determined by osmometer to be approximately 321 to 322.7 mOsm/kg.3797
Sodium Content
The sodium content of acyclovir sodium concentrate for injection is approximately 5.1 mg/mL.3795
Acyclovir sodium is administered by intravenous infusion over a period of 1 hour following dilution to a final concentration of 7 mg/mL or less.3795; 3796 Rapid intravenous administration and administration by other routes must be avoided.3795; 3796
Intact vials of acyclovir sodium concentrate for injection should be stored at controlled room temperature.3795 Diluted solutions for infusion should be used within 24 hours.3795
Intact vials of acyclovir sodium lyophilized powder should be stored at controlled room temperature.3796 The reconstituted solution should be used within 12 hours.3796 Refrigeration of the reconstituted solution may cause a precipitate which will redissolve at room temperature.3796 Diluted solutions for infusion should be used within 24 hours.3795; 3796 Precipitation has been observed in acyclovir sodium infusions in polyvinyl chloride (PVC) containers after a few days’ storage at room temperature.2190
Precipitation
Short-term refrigerated storage of acyclovir sodium admixtures with concentrations exceeding 1 mg/mL may result in formation of a precipitate that redissolves upon warming to room temperature. However, such solutions should be used immediately after warming to room temperature because of the subsequent appearance of persistent microprecipitates.2098
Physical instability is the principal limitation to long-term storage of acyclovir sodium admixtures. Persistent subvisual microprecipitate formation as well as frank persistent precipitation may occur in variable time periods. Such precipitation has been reported to occur after as little as 7 days and in varying time periods throughout a 35-day observation period; the appearance of a precipitate is not precisely predictable.2098
The formation of large amounts of subvisual particulates has been attributed to an interaction of the highly alkaline acyclovir sodium solution with PVC containers. Some increase in the number of particulates was observed in as little as 1 day, with substantial increases in 7 days. When packaged in ethylene vinyl acetate (EVA) containers, no significant increase in subvisual particulates occurs, even after 28 days of storage.2190
Freezing Solutions
Acyclovir (GlaxoSmithKline; Hospira) 5 mg/mL in sodium chloride 0.9% in polyolefin bags was found to be physically stable with less than 10% loss reported when frozen at -20°C for 90 days followed by thawing in a microwave oven and subsequent storage at 2 to 8°C for 15 days.3300
Syringes
Acyclovir sodium (American Pharmaceutical Partners) 10 mg/mL in sodium chloride 0.9% and packaged in polypropylene syringes (Becton Dickinson) was found to be stable for 30 days at room temperature but precipitated in 5 days under refrigeration.2558
Sorption
Acyclovir sodium was shown not to exhibit sorption to PVC, polyethylene, and glass containers as well as elastomeric reservoirs.2014; 2289
Elastomeric Reservoir Pumps
Acyclovir sodium (Hospira Australia) in sodium chloride 0.9%, prepared as 200, 2400, or 4500 mg of acyclovir in 240 mL (0.833, 10, or 18.75 mg/mL, respectively) in Easypump II (B Braun) and Accufuser (Vygon UK) elastomeric reservoir pumps, was stored at room temperature 20°C for 14 days followed by exposure to 32°C for up to 24 hours.3995 The solutions were protected from light throughout the study.3995 The 200 and 2400 mg in 240 mL solutions were physically stable with little loss of acyclovir after storage for 14 days at 20°C followed by 24 hours at 32°C.3995 The 4500 mg in 240 mL solution was physically stable with no loss after 14 days at 20°C; however, massive precipitation occurred with substantial acyclovir loss upon exposure of the solution to 32°C.3995
Central Venous Catheter
Acyclovir sodium (GlaxoWellcome) 1 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
For a list of references cited in the text of this monograph, search the monograph titled References.