Diltiazem hydrochloride is available as a 5-mg/mL solution in 5-mL (25-mg), 10-mL (50-mg), and 25-mL (125-mg) single-use vials.2875 Also present in each mL of solution are citric acid hydrous 0.75 mg, sodium citrate dihydrate 0.65 mg, sorbitol solution 71.4 mg, and water for injection.2875 Sodium hydroxide or hydrochloric acid is used to adjust the pH.2875
Diltiazem hydrochloride also is available as a lyophilized powder in 100-mg single-use ADD-Vantage vials.2876 Each ADD-Vantage vial also contains mannitol base 75 mg.2876 ADD-Vantage vials of diltiazem hydrochloride should be prepared with 100 mL of dextrose 5% or sodium chloride 0.9% in ADD-Vantage diluent bags.2876
pH
From 3.7 to 4.1.2875
Diltiazem hydrochloride in single-use vials is administered by direct intravenous injection over 2 minutes and by continuous intravenous infusion after dilution.2875
Following reconstitution using ADD-Vantage diluent bags, ADD-Vantage vials are intended for continuous intravenous infusion and should not be used for direct intravenous injection.2876
Intact vials of the liquid injection should be stored under refrigeration and protected from freezing.2875 Diltiazem hydrochloride may be stored for up to 1 month at room temperature but should then be destroyed.2875
Intact ADD-Vantage vials of diltiazem hydrochloride should be stored at controlled room temperature and protected from freezing.2876 Reconstituted ADD-Vantage diltiazem hydrochloride injection is stable for 24 hours at controlled room temperature or under refrigeration.2876
pH Effects
An increased rate of diltiazem hydrochloride hydrolysis occurs with increasing pH. Hydrolysis was lowest at pH 5 and 6 but increased substantially at pH 7 and 8. Diltiazem hydrochloride 100 mcg/mL in sodium chloride 0.9% with a pH between 5 and 6 exhibited no loss in 24 hours. Buffered to pH 7, losses of 3 to 4% in 24 hours were found.1915
Light Effects
Diltiazem hydrochloride reconstituted with distilled water to a concentration of 10 mg/mL was exposed to UVA-UVB radiation with a solar simulator for 28 hours. Only 5.6% degradation occurred under this intense light exposure. The drug maintained adequate stability and light protection was not required.2432
Freezing Solutions
Diltiazem hydrochloride (Baxter) 1 mg/mL in dextrose 5% was stored in polyolefin bags and frozen at -20°C.2874 The solution was physically stable and demonstrated less than 3% loss after 30 days of storage followed by warming to room temperature.2874
Sorption
A pH-dependent loss of diltiazem hydrochloride occurs due to sorption to polyvinyl chloride (PVC) containers and administration sets. Diltiazem hydrochloride 100 mcg/mL in sodium chloride 0.9% buffered to neutrality exhibits a loss of 11% in 24 hours in PVC containers but only 3 to 4% in glass and polypropylene containers. Similar results were found with PVC administration sets. Buffered to pH 8, diltiazem hydrochloride concentration was initially reduced to about 83% when delivered at 0.52 mL/min through a 100-cm PVC administration set. At pH 6 and 7, initial losses were much less, about 1 and 5%, respectively. Delivered diltiazem hydrochloride returned to full concentration in less than 1 hour at pH 6 and 7 but at pH 8 was only about 93% in 2 hours.1915
Diltiazem hydrochloride 0.05 mg/mL in dextrose 5% and sodium chloride 0.9% packaged in PVC, polyethylene, and glass containers exhibited little or no loss due to sorption to any of the container types when stored at 4 and 22°C for 24 hours protected from light.2289
Diltiazem hydrochloride (Synthelabo) 1 g/L in dextrose 5% and in sodium chloride 0.9% was evaluated for loss due to sorption to a variety of polymer container types compared to glass containers. No significant loss due to sorption was found at 21°C after 48 hours of contact time to PVC and polyethylene containers and 24 hours of contact time to polyamide containers.274
Similarly, no significant loss of diltiazem hydrochloride occurred from 1-g/L solutions in dextrose 5% and in sodium chloride 0.9% in cellulose propionate (Abbott), butadiene styrene (B. Braun), and metacrylate butadiene styrene (Avon) burettes for 24 hours at 21°C and when delivered over 5 hours through PVC (Abbott and Baxter), PVC/polyethylene double polymer (Abbott), and polybutadiene (Avon) administration tubing.274
Filtration
Cellulose ester filters (B. Braun and Millipore) were found to result in a temporary reduction in the concentration of delivered diltiazem hydrochloride from a 1-g/L solution in sodium chloride 0.9%. The concentration of delivered diltiazem hydrochloride returned to near 100% after about 1 to 2 hours of infusion through the filter. No reduction in delivered concentration was found if dextrose 5% was used as the vehicle. No loss occurred in either infusion solution with polyamide (Pall) filters.274
Standardize 4 Safety
One or more standardized concentrations for this drug have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. (See Standardize 4 Safety in Users Guide.) Recommendations developed to date through this initiative are available at www.ashp.org/pharmacy-practice/standardize-4-safety-initiative.
Table 1: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Diltiazem3636
| Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
| Adults | 1 mg/mL | mg/hour |
For a list of references cited in the text of this monograph, search the monograph titled References.