Argatroban concentrate for injection is available in 2.5-mL single-use vials containing 250 mg of the drug.3186 Several different formulations of the concentrate for injection are available and excipients vary among them.3186; 3190; 3191 Each mL of the concentrate for injection (GlaxoSmithKline) also contains D-sorbitol 300 mg and dehydrated alcohol 400 mg in water for injection.3186 Each mL of the concentrate for injection (Fresenius Kabi) also contains propylene glycol 954 mg.3190 Each mL of the concentrate for injection (West-Ward) also contains propylene glycol 1300 mg and dehydrated alcohol 760 mg.3191 The concentrate for injection must be diluted 100-fold in sodium chloride 0.9%, dextrose 5%, or Ringer’s injection, lactated to yield a final concentration of 1 mg/mL.3186 The solution should be mixed thoroughly after dilution by repeated inversion of the infusion bag for 1 minute.3186 Slight haziness may form due to transient microprecipitation, however, the microprecipitates should dissolve rapidly with mixing.3186 Use of room temperature diluent is recommended for dilution as colder temperatures can slow down the dissolution rate of precipitates.3186 The diluted solution for infusion must be clear for administration.3186
Argatroban also is available as a ready-to-use solution of 1 mg/mL of argatroban in 50- and 125-mL single-use vials and 250-mL single-use polyolefin bags.3187; 3188; 3189 Each mL of solution in the 50-mL (50-mg) vial also contains lactobionic acid 2 mg, L-methionine 2 mg, sodium chloride 8 mg, and sodium hydroxide to adjust the pH in water for injection.3187 Each mL of solution in the 125-mL (125-mg) vial and 250-mL (250-mg) bag also contains sodium chloride 9 mg and sorbitol 3 mg in water for injection.3188; 3189 The ready-to-use solution should not be diluted prior to administration.3187; 3188; 3189
pH
The pH of the concentrate for injection diluted to a concentration of 1 mg/mL for infusion and the 1-mg/mL ready-to-use solution in 125-mL vials and 250-mL bags ranges from 3.2 to 7.5.3186; 3188; 3189 The pH of the 1-mg/mL ready-to-use solution in 50-mL vials is approximately 8.8.3187
Tonicity
The 1-mg/mL ready-to-use solution of argatroban in 125-mL vials and 250-mL bags is isotonic.3188; 3189
Argatroban solutions of 1 mg/mL are administered by continuous intravenous infusion.3186; 3187; 3188; 3189 For certain indications, an initial bolus injection of the 1-mg/mL solution should be administered over 3 to 5 minutes through a large bore intravenous line; subsequent additional bolus injections of the 1-mg/mL solution may be warranted for dosage adjustment.3186; 3187; 3188; 3189 Specific labeling should be consulted for further dosage and administration details.
Vials of the ready-to-use solution of argatroban may be inverted and connected to an infusion set for administration.3187; 3188
Argatroban concentrate for injection and ready-to-use solutions are clear and colorless to pale yellow in appearance.3186; 3187; 3188; 3189 The concentrate for injection is slightly viscous.3186 Intact vials of the concentrate for injection and intact vials and bags of the ready-to-use solutions should be stored at controlled room temperature and retained in the original carton to protect from light.3186; 3187; 3188; 3189 At least one manufacturer states that its vials of the ready-to-use solution should not be refrigerated;3187 all manufacturers of argatroban state that freezing should be avoided.3186; 3187; 3188; 3189
The solution for infusion should be visually inspected for particulate matter and discoloration prior to administration; if precipitation is present or if cloudiness occurs, the solution should not be used and should be discarded.3186; 3187; 3188; 3189
Several manufacturers of the concentrate for injection state that solutions of argatroban diluted for infusion as recommended are stable for 24 hours at 20 to 25°C in ambient indoor light, and therefore, light-resistant measures (e.g., foil protection of the intravenous line) are unnecessary.3186; 3191 Solutions diluted for infusion should not be exposed to direct sunlight.3186
Sorption
No substantial potency losses have been reported following simulated delivery of the diluted solution for infusion through intravenous tubing.3186
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 Argatroban3635; 3636
| Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
| Adults | 1 mg/mL | mcg/kg/minute (note dosing units differ from concentration units) |
| Pediatric patients (50 kg) | 1 mg/mL | mcg/kg/minute (note dosing units differ from concentration units) |
For a list of references cited in the text of this monograph, search the monograph titled References.